Design and synthesis of novel conformationally constrained 7,12-dihydrodibenzo[b,h][1,6] naphthyridine and 7H-Chromeno[3,2-c] quinoline derivatives as topoisomerase I inhibitors: In vitro screening, molecular docking and ADME predictions
Bioorg Chem. 2021 Jul 16;115:105174. doi: 10.1016/j.bioorg.2021.105174. Online ahead of print.ABSTRACTNovel non-camptothecin (non-CPT) class of conformationally constrained, hitherto unknown 7,12-dihydrodibenzo[b,h][1,6] naphthyridine and 7H-Chromeno[3,2-c] quinoline derivatives have been designed, synthesized and evaluated for anti-cancer activity. In vitro anti-proliferation evaluation against human cancer cell lines (A549 and MCF-7) exhibited significant cytotoxicity. Among the derivatives (8-24), 8 (IC50 0.44 μM and IC50 0.62 μM) and 12 (IC50 0.69 μM and IC50 0.54 μM) were identified as the most promising c...
Source: Bioorganic Chemistry - July 27, 2021 Category: Chemistry Authors: Ramakant A Kardile Aniket P Sarkate Avinash S Borude Rajendra S Mane Deepak K Lokwani Shailee V Tiwari Rajaram Azad Prasad V L S Burra Shankar R Thopate Source Type: research

Design, synthesis, molecular docking and in silico ADMET profile of pyrano[2,3-d]pyrimidine derivatives as antimicrobial and anticancer agents
Bioorg Chem. 2021 Jul 22;115:105186. doi: 10.1016/j.bioorg.2021.105186. Online ahead of print.ABSTRACTPyrano[2,3-d]pyrimidine derivatives were synthesized by treating cyclic compounds containing active methylene group with aldehyde and malononitrile in butanol. The behavior of pyrano[2,3-d]pyrimidine towards some electrophlies namely triethylorthoformate followed by nitrogen nucleophiles as isobutylamine, urea, phenylthiourea, p-toluidine, o-phenylenediamine, o-aminophenol, 2-amino-4-methyl-pyridine and acetic acid with the aim of obtaining some interesting non-mixed heterocyclic compounds. All synthesized compounds to som...
Source: Bioorganic Chemistry - July 27, 2021 Category: Chemistry Authors: Nour E A Abd El-Sattar Khaled El-Adl Maher A El-Hashash Samir A Salama Mostafa M Elhady Source Type: research

Nucleus-targeting imaging and enhanced cytotoxicity based on naphthalimide derivatives
Bioorg Chem. 2021 Jul 20;115:105188. doi: 10.1016/j.bioorg.2021.105188. Online ahead of print.ABSTRACTOrganelles possess critical biological effects in cellular processes. However, the relationship between organelle targeting and antitumour activity is a challenging issue. In this paper, a number of amide/acylhydrazine modified naphthalimide derivatives were designed and synthesized. Interestingly, amide modified naphthalimide derivatives NI-A-NH and NI-C-NH with (R)-piperdine and (S)-pyrrolidine functionalization exhibited enhanced cytotoxicity compared with acylhydrazine modified derivatives NI-A-2NH and NI-C-2NH. Howeve...
Source: Bioorganic Chemistry - July 27, 2021 Category: Chemistry Authors: Shan-Shan Wang Shao-Ying Du Xu He Yu-Ming Qi Xiao-Liu Li Rui-Xue Rong Zhi-Ran Cao Ke-Rang Wang Source Type: research

Development of coumarin-thiosemicarbazone hybrids as aldose reductase inhibitors: Biological assays, molecular docking, simulation studies and ADME evaluation
Bioorg Chem. 2021 Jul 13;115:105164. doi: 10.1016/j.bioorg.2021.105164. Online ahead of print.ABSTRACTThe over expression of aldose reductase (ALR2) in the state of hyperglycemia causes the conversion of glucose into sorbitol and initiates polyol pathway. Accumulation of sorbitol in insulin insensitive tissue like peripheral nerves, glomerulus and eyes, induces diabetic complications like neuropathy, nephropathy and retinopathy. For the treatment of diabetic complications, the inhibition of aldose reductase (ALR2) is a promising approach. A series of coumarin-based thiosemicarbazone derivatives was synthesized as potential...
Source: Bioorganic Chemistry - July 27, 2021 Category: Chemistry Authors: Aqeel Imran Muhammad Tariq Shehzad Taha Al Adhami Khondaker Miraz Rahman Dilawar Hussain Rima D Alharthy Zahid Shafiq Jamshed Iqbal Source Type: research

Absolute configuration of polypropionate derivatives: Decempyrones A-J and their MptpA inhibition and anti-inflammatory activities
Bioorg Chem. 2021 Jul 19;115:105156. doi: 10.1016/j.bioorg.2021.105156. Online ahead of print.ABSTRACTUnder guidance of 1H NMR, ten new polypropionate derivatives, decempyrones A-J (1-10) along with two known analogues (11 and 12), were isolated from the marine-derived fungusFusarium decemcellulare SYSU-MS6716. The planar structures were elucidated on the basis of extensive spectroscopic analyses (1D and 2D NMR, and HR-ESIMS). The absolute configuration of the chiral centers in the side chain is a major obstacle for the structure identification of natural polypropionate derivatives. Herein, the J-based configurational anal...
Source: Bioorganic Chemistry - July 27, 2021 Category: Chemistry Authors: Heng Guo Qilin Wu Dongni Chen Minghua Jiang Bin Chen Yongjun Lu Jing Li Lan Liu Senhua Chen Source Type: research

Selective targeting of cancer cells using a hydrogen peroxide-activated Hsp90 inhibitor
Bioorg Chem. 2021 Jul 21;115:105195. doi: 10.1016/j.bioorg.2021.105195. Online ahead of print.ABSTRACTHeat shock protein 90 (Hsp90) plays an important role in cancer cell proliferation, survival, and migration by regulating the maturation and stabilization of numerous oncoproteins. Despite significant efforts in developing Hsp90 inhibitors, none of these have been approved for clinical use, mostly due to toxicity, such as liver, cardiac, and retinal toxicity. To avoid undesirable toxicity, we herein report a hydrogen peroxide-activated Hsp90 inhibitor, Boro-BZide (3), which is capable of selectively targeting cancer cells ...
Source: Bioorganic Chemistry - July 27, 2021 Category: Chemistry Authors: Yong Jin Oh Sun You Park Young Ho Seo Source Type: research

Design, synthesis and biological evaluation of novel 5-(imidazolyl-methyl) thiazolidinediones as antidiabetic agents
Bioorg Chem. 2021 Jul 13;115:105162. doi: 10.1016/j.bioorg.2021.105162. Online ahead of print.ABSTRACTA newly designed series of imidazolyl-methyl- l-2,4-thiazolidinediones 9 (a-m) were synthesized and In Silico studies were carried out to rationalize their anti-diabetic activity. Generally, all newly synthesized thiazolidinediones had anti-hyperglycemic activity compared with a diabetic-control group, without toxicity in 3T3 cells (viability ≥ 90%). These studies revealed that the compounds 9e and 9b (11∗10-6mol/kg) lowered blood glucose more effectively when compared to pioglitazone at the same dose. Following ...
Source: Bioorganic Chemistry - July 27, 2021 Category: Chemistry Authors: Neda Shakour Amirhossein Sahebkar Gholamreza Karimi Maryam Paseban Aida Tasbandi Fatemeh Mosaffa Zahra Tayarani-Najaran Razieh Ghodsi Farzin Hadizadeh Source Type: research

Synthesis of new 2-(thiazol-4-yl)thiazolidin-4-one derivatives as potential anti-mycobacterial agents
Bioorg Chem. 2021 Jul 21;115:105192. doi: 10.1016/j.bioorg.2021.105192. Online ahead of print.ABSTRACTTo search for potent antimycobacterial lead compounds, a new series of 3-substituted phenyl-2-(2-(substituted phenyl)thiazol-4-yl) thiazolidin-4-one (5a-t) derivatives have been synthesized by the condensation of 2-substituted phenyl thiazole-4-carbaldehyde with aromatic amine followed by cyclocondensation with thioglycolic acid. The structure of the newly synthesized 2-(thiazol-4-yl)thiazolidin-4-one derivatives were characterized by the spectroscopic analysis. The synthesized compounds were screened for antimycobacterial...
Source: Bioorganic Chemistry - July 27, 2021 Category: Chemistry Authors: Yogita K Abhale Abhijit Shinde Monika Shelke Laxman Nawale Dhiman Sarkar Pravin C Mhaske Source Type: research

Discovery of small molecule acting as multitarget inhibitor of colorectal cancer by simultaneous blocking of the key COX-2, 5-LOX and PIM-1 kinase enzymes
In conclusion, compound 5g, of simple chemical structure, achieved the target goal of inhibiting three targets leading to inhibition of human CRC cell proliferation. It inhibited the target key enzymes COX-2, 5-LOX and PIM-1\2 kinase in vitro. Besides, it revealed in vitro inhibition of cell proliferation in cancer cell lines via activation of caspase 3\7 dependent-apoptosis in human CRC cell lines. In addition, it elicited in vivo anti-inflammatory activity in formalin-induced paw edema test and in vivo oral safety in gastric ulcerogenic activity test.PMID:34303896 | DOI:10.1016/j.bioorg.2021.105171 (Source: Bioorganic Chemistry)
Source: Bioorganic Chemistry - July 25, 2021 Category: Chemistry Authors: Mostafa M M El-Miligy Ahmed K Al-Kubeisi Saad R El-Zemity Rasha A Nassra Marwa M Abu-Serie Aly A Hazzaa Source Type: research

Structurally diversified ent-kaurane and abietane diterpenoids from the stems of Tripterygium wilfordii and their anti-inflammatory activity
Bioorg Chem. 2021 Jul 20;115:105178. doi: 10.1016/j.bioorg.2021.105178. Online ahead of print.ABSTRACTFour undescribed ent-kaurane diterpenoids, wilkaunoids A - D (1-4), and three undescribed abietane diterpenoids, wilabinoids A - C (13-15), along with thirteen known ones (5-12 and 16-20), were isolated from Tripterygium wilfordii. Their structures were elucidated by extensive spectroscopic methods, electroniccirculardichroism calculation, and X-ray diffraction analysis. Compounds 1 and 2 were a pair of C-19 epimers of ent-kaurane diterpenoids, featuring a rare 19,20-epoxy-19,20-dimethoxy-kaurane fragment. Compound 3 posse...
Source: Bioorganic Chemistry - July 25, 2021 Category: Chemistry Authors: Xiao-Qiong Zhou Si-Qi Li Cai-Ceng Liao Wei-Feng Dai Kai-Rui Rao Xiu-Rong Ma Rong-Tao Li Xuan-Qin Chen Source Type: research

Design, synthesis and evaluation of tetrahydrocarbazole derivatives as potential hypoglycemic agents
Bioorg Chem. 2021 Jul 17;115:105172. doi: 10.1016/j.bioorg.2021.105172. Online ahead of print.ABSTRACTTwo series of tetrahydrocarbazole derivatives have been designed and synthesized based on ZG02, a promising candidate developed in our previous studies. The newly prepared compounds were screened for glucose consumption activity in HepG2 cell lines. Aza-tetrahydrocarbazole compound 12b showed the most potent hypoglycemic activity with a 45% increase in glucose consumption when compared to the solvent control, which had approximately 1.2-fold higher activity than the positive control compounds (metformin and ZG02). An inves...
Source: Bioorganic Chemistry - July 25, 2021 Category: Chemistry Authors: Li-Li Wang Yao Du Shu-Min Li Fei Cheng Na-Na Zhang Rui Chen Xing Cui Sheng-Gang Yang Ling-Ling Fan Jian-Ta Wang Bing Guo Hao-Shu Wu Ji-Quan Zhang Lei Tang Source Type: research

Discovery of small molecule acting as multitarget inhibitor of colorectal cancer by simultaneous blocking of the key COX-2, 5-LOX and PIM-1 kinase enzymes
In conclusion, compound 5g, of simple chemical structure, achieved the target goal of inhibiting three targets leading to inhibition of human CRC cell proliferation. It inhibited the target key enzymes COX-2, 5-LOX and PIM-1\2 kinase in vitro. Besides, it revealed in vitro inhibition of cell proliferation in cancer cell lines via activation of caspase 3\7 dependent-apoptosis in human CRC cell lines. In addition, it elicited in vivo anti-inflammatory activity in formalin-induced paw edema test and in vivo oral safety in gastric ulcerogenic activity test.PMID:34303896 | DOI:10.1016/j.bioorg.2021.105171 (Source: Bioorganic Chemistry)
Source: Bioorganic Chemistry - July 25, 2021 Category: Chemistry Authors: Mostafa M M El-Miligy Ahmed K Al-Kubeisi Saad R El-Zemity Rasha A Nassra Marwa M Abu-Serie Aly A Hazzaa Source Type: research

Structurally diversified ent-kaurane and abietane diterpenoids from the stems of Tripterygium wilfordii and their anti-inflammatory activity
Bioorg Chem. 2021 Jul 20;115:105178. doi: 10.1016/j.bioorg.2021.105178. Online ahead of print.ABSTRACTFour undescribed ent-kaurane diterpenoids, wilkaunoids A - D (1-4), and three undescribed abietane diterpenoids, wilabinoids A - C (13-15), along with thirteen known ones (5-12 and 16-20), were isolated from Tripterygium wilfordii. Their structures were elucidated by extensive spectroscopic methods, electroniccirculardichroism calculation, and X-ray diffraction analysis. Compounds 1 and 2 were a pair of C-19 epimers of ent-kaurane diterpenoids, featuring a rare 19,20-epoxy-19,20-dimethoxy-kaurane fragment. Compound 3 posse...
Source: Bioorganic Chemistry - July 25, 2021 Category: Chemistry Authors: Xiao-Qiong Zhou Si-Qi Li Cai-Ceng Liao Wei-Feng Dai Kai-Rui Rao Xiu-Rong Ma Rong-Tao Li Xuan-Qin Chen Source Type: research

Design, synthesis and evaluation of tetrahydrocarbazole derivatives as potential hypoglycemic agents
Bioorg Chem. 2021 Jul 17;115:105172. doi: 10.1016/j.bioorg.2021.105172. Online ahead of print.ABSTRACTTwo series of tetrahydrocarbazole derivatives have been designed and synthesized based on ZG02, a promising candidate developed in our previous studies. The newly prepared compounds were screened for glucose consumption activity in HepG2 cell lines. Aza-tetrahydrocarbazole compound 12b showed the most potent hypoglycemic activity with a 45% increase in glucose consumption when compared to the solvent control, which had approximately 1.2-fold higher activity than the positive control compounds (metformin and ZG02). An inves...
Source: Bioorganic Chemistry - July 25, 2021 Category: Chemistry Authors: Li-Li Wang Yao Du Shu-Min Li Fei Cheng Na-Na Zhang Rui Chen Xing Cui Sheng-Gang Yang Ling-Ling Fan Jian-Ta Wang Bing Guo Hao-Shu Wu Ji-Quan Zhang Lei Tang Source Type: research

Discovery of small molecule acting as multitarget inhibitor of colorectal cancer by simultaneous blocking of the key COX-2, 5-LOX and PIM-1 kinase enzymes
In conclusion, compound 5g, of simple chemical structure, achieved the target goal of inhibiting three targets leading to inhibition of human CRC cell proliferation. It inhibited the target key enzymes COX-2, 5-LOX and PIM-1\2 kinase in vitro. Besides, it revealed in vitro inhibition of cell proliferation in cancer cell lines via activation of caspase 3\7 dependent-apoptosis in human CRC cell lines. In addition, it elicited in vivo anti-inflammatory activity in formalin-induced paw edema test and in vivo oral safety in gastric ulcerogenic activity test.PMID:34303896 | DOI:10.1016/j.bioorg.2021.105171 (Source: Bioorganic Chemistry)
Source: Bioorganic Chemistry - July 25, 2021 Category: Chemistry Authors: Mostafa M M El-Miligy Ahmed K Al-Kubeisi Saad R El-Zemity Rasha A Nassra Marwa M Abu-Serie Aly A Hazzaa Source Type: research

Structurally diversified ent-kaurane and abietane diterpenoids from the stems of Tripterygium wilfordii and their anti-inflammatory activity
Bioorg Chem. 2021 Jul 20;115:105178. doi: 10.1016/j.bioorg.2021.105178. Online ahead of print.ABSTRACTFour undescribed ent-kaurane diterpenoids, wilkaunoids A - D (1-4), and three undescribed abietane diterpenoids, wilabinoids A - C (13-15), along with thirteen known ones (5-12 and 16-20), were isolated from Tripterygium wilfordii. Their structures were elucidated by extensive spectroscopic methods, electroniccirculardichroism calculation, and X-ray diffraction analysis. Compounds 1 and 2 were a pair of C-19 epimers of ent-kaurane diterpenoids, featuring a rare 19,20-epoxy-19,20-dimethoxy-kaurane fragment. Compound 3 posse...
Source: Bioorganic Chemistry - July 25, 2021 Category: Chemistry Authors: Xiao-Qiong Zhou Si-Qi Li Cai-Ceng Liao Wei-Feng Dai Kai-Rui Rao Xiu-Rong Ma Rong-Tao Li Xuan-Qin Chen Source Type: research

Design, synthesis and evaluation of tetrahydrocarbazole derivatives as potential hypoglycemic agents
Bioorg Chem. 2021 Jul 17;115:105172. doi: 10.1016/j.bioorg.2021.105172. Online ahead of print.ABSTRACTTwo series of tetrahydrocarbazole derivatives have been designed and synthesized based on ZG02, a promising candidate developed in our previous studies. The newly prepared compounds were screened for glucose consumption activity in HepG2 cell lines. Aza-tetrahydrocarbazole compound 12b showed the most potent hypoglycemic activity with a 45% increase in glucose consumption when compared to the solvent control, which had approximately 1.2-fold higher activity than the positive control compounds (metformin and ZG02). An inves...
Source: Bioorganic Chemistry - July 25, 2021 Category: Chemistry Authors: Li-Li Wang Yao Du Shu-Min Li Fei Cheng Na-Na Zhang Rui Chen Xing Cui Sheng-Gang Yang Ling-Ling Fan Jian-Ta Wang Bing Guo Hao-Shu Wu Ji-Quan Zhang Lei Tang Source Type: research

A new ferroptosis inhibitor, isolated from Ajuga nipponensis, protects neuronal cells via activating NRF2-antioxidant response elements (AREs) pathway
This study reveals that ADC, as a new ferroptosis inhibitor, is a promising lead compound for the development of drugs against ferroptosis-related neurological diseases.PMID:34303035 | DOI:10.1016/j.bioorg.2021.105177 (Source: Bioorganic Chemistry)
Source: Bioorganic Chemistry - July 24, 2021 Category: Chemistry Authors: Qingyun Tan Yuying Fang Xing Peng Huihao Zhou Jun Xu Qiong Gu Source Type: research

Biphenyl substituted lysine derivatives as recognition elements for the matrix metalloproteinases MMP-2 and MMP-9
In this study, we combined experimental results obtained by a kinetic fluorogenic peptide substrate cleavage assay with molecular modeling studies in order to assess the ability of the probe to bind to their target enzymes. The synthesized biphenyl substituted lysine derivatives showed IC50-values in the low nanomolar concentration range against MMP-2 (ligands 3a-d: 3 nM to 8 µM, ligands 4a-d: 45 nM to 350 µM) and low micromolar range against MMP-9 (ligands 3a-d: 350 nM to 60 µM, ligands 4a-d: 5 µM to 600 µM), with a selectivity up to more than 160-fold for MMP-2. The experimental results corr...
Source: Bioorganic Chemistry - July 24, 2021 Category: Chemistry Authors: Arno Kirchhain Asta Zubrien ė Visvaldas Kairys Federico Vivaldi Andrea Bonini Denise Biagini Delio Santalucia Daumantas Matulis Fabio Di Francesco Source Type: research

Integrating systematic pharmacology-based strategy and experimental validation to explore the synergistic pharmacological mechanisms of Guanxin V in treating ventricular remodeling
CONCLUSION: GXV could relieve and reverse VR through anti-apoptosis and anti-fibrosis effects predicted by systematic pharmacology and validated by molecular docking and molecular experiments. Our study deepens the understanding of the molecular mechanisms of GXV in treating VR.PMID:34303037 | DOI:10.1016/j.bioorg.2021.105187 (Source: Bioorganic Chemistry)
Source: Bioorganic Chemistry - July 24, 2021 Category: Chemistry Authors: Bo Liang Yi Liang Rui Li Hui Zhang Ning Gu Source Type: research

New N-(1,3,4-thiadiazol-2-yl)furan-2-carboxamide derivatives as potential inhibitors of the VEGFR-2
Bioorg Chem. 2021 Jul 16;115:105176. doi: 10.1016/j.bioorg.2021.105176. Online ahead of print.ABSTRACTThe present study reports the synthesis and biological evaluation of a new series of novel N-(1,3,4-thiadiazol-2-yl)furan-2-carboxamide derivatives. The reactions were executed under both conventional and microwave irradiation conditions. An enhancement in the synthetic yields and rates was observed when the reactions were carried out under the microwave compared with the classical conditions. The structures of the products were ascertained by different analytical and spectral analyses. The antiproliferative activities wer...
Source: Bioorganic Chemistry - July 24, 2021 Category: Chemistry Authors: Mohamed H Hekal Paula S Farag Magdy M Hemdan Wael M El-Sayed Source Type: research

Identification of novel anti-cancer agents by the synthesis and cellular screening of a noscapine-based library
Bioorg Chem. 2021 Jun 30;115:105135. doi: 10.1016/j.bioorg.2021.105135. Online ahead of print.ABSTRACTNoscapine is a natural product first isolated from the opium poppy (Papaver somniferum L.) with anticancer properties. In this work, we report the synthesis and cellular screening of a noscapine-based library. A library of novel noscapine derivatives was synthesized with modifications in the isoquinoline and phthalide scaffolds. The so generated library, consisting of fifty-seven derivatives of the natural product noscapine, was tested against MDA-MB-231 breast cancer cells in a cellular proliferation assay (with a Z'> ...
Source: Bioorganic Chemistry - July 24, 2021 Category: Chemistry Authors: Faezeh Nemati Iris Bischoff-Kont Peyman Salehi Samad Nejad-Ebrahimi Maryam Mohebbi Morteza Bararjanian Nasim Hadian Zahra Hassanpour Yvonne Jung Sofie Schaerlaekens Daniel Lucena-Agell Mar ía A Oliva Robert F ürst Hamid R Nasiri Source Type: research

Design, Hemiysnthesis, crystal structure and anticancer activity of 1, 2, 3-triazoles derivatives of totarol
Bioorg Chem. 2021 Jul 14;115:105165. doi: 10.1016/j.bioorg.2021.105165. Online ahead of print.ABSTRACTA new series of diverse triazoles linked to the hydroxyl group of totarol were synthesized using click chemistry approach. The structures of these compounds were elucidated by HRMS, IR and NMR spectroscopy. The structure of compound 3 g was also confirmed by x-ray single crystal diffraction. The cytotoxicity of these compounds was evaluated by the MTT method against four cancer cell lines, including fibrosarcoma HT-1080, lung carcinoma A-549 and breast adenocarcinoma (MDA-MB-231 and MCF-7), and the results indicated that a...
Source: Bioorganic Chemistry - July 23, 2021 Category: Chemistry Authors: Yassine Laamari Ali Oubella Abdoullah Bimoussa Az-Eddine El Mansouri El Mostafa Ketatni Olivier Mentre My Youssef Ait Itto Hamid Morjani Mostafa Khouili Aziz Auhmani Source Type: research

Discovery of novel inhibitors of human phosphoglycerate dehydrogenase by activity-directed combinatorial chemical synthesis strategy
Bioorg Chem. 2021 Jul 8;115:105159. doi: 10.1016/j.bioorg.2021.105159. Online ahead of print.ABSTRACTSerine, the source of the one-carbon units essential for de novo purine and deoxythymidine synthesis plays a crucial role in the growth of cancer cells. Phosphoglycerate dehydrogenase (PHGDH) which catalyzes the first, rate-limiting step in de novo serine biosynthesis has become a promising target for the cancer treatment. Here we identified H-G6 as a potential PHGDH inhibitor from the screening of an in-house small molecule library based on the enzymatic assay. We adopted activity-directed combinatorial chemical synthesis ...
Source: Bioorganic Chemistry - July 23, 2021 Category: Chemistry Authors: Xia Zhou Yuping Tan Kun Gou Lei Tao Yuan Luo Yue Zhou Zeping Zuo Qingxiang Sun Youfu Luo Yinglan Zhao Source Type: research

Benzimidazole analogues as efficient arsenals in war against methicillin-resistance staphylococcus aureus (MRSA) and its SAR studies
Bioorg Chem. 2021 Jul 17;115:105175. doi: 10.1016/j.bioorg.2021.105175. Online ahead of print.ABSTRACTSmall molecule based inhibitors development is a growing field in medicinal chemistry. In recent years, different heterocyclic derivatives have been designed to counter the infections caused by multi-drug resistant bacteria. Indeed, small molecule inhibitors can be employed as an efficient antibacterial agents with different mechanism of action. Methicillin-resistant Staphylococcus aureus (MRSA) is becoming lethal to mankind due to easy transmission mode, rapid resistance development to existing antibiotics and affect diff...
Source: Bioorganic Chemistry - July 23, 2021 Category: Chemistry Authors: Gao-Feng Zha Habbanakuppe D Preetham Shobith Rangappa Kothanahally S Sharath Kumar Yarabahally R Girish Kadalipura P Rakesh Milad Ashrafizadeh Ali Zarrabi Kanchugarakoppal S Rangappa Source Type: research

Design, Hemiysnthesis, crystal structure and anticancer activity of 1, 2, 3-triazoles derivatives of totarol
Bioorg Chem. 2021 Jul 14;115:105165. doi: 10.1016/j.bioorg.2021.105165. Online ahead of print.ABSTRACTA new series of diverse triazoles linked to the hydroxyl group of totarol were synthesized using click chemistry approach. The structures of these compounds were elucidated by HRMS, IR and NMR spectroscopy. The structure of compound 3 g was also confirmed by x-ray single crystal diffraction. The cytotoxicity of these compounds was evaluated by the MTT method against four cancer cell lines, including fibrosarcoma HT-1080, lung carcinoma A-549 and breast adenocarcinoma (MDA-MB-231 and MCF-7), and the results indicated that a...
Source: Bioorganic Chemistry - July 23, 2021 Category: Chemistry Authors: Yassine Laamari Ali Oubella Abdoullah Bimoussa Az-Eddine El Mansouri El Mostafa Ketatni Olivier Mentre My Youssef Ait Itto Hamid Morjani Mostafa Khouili Aziz Auhmani Source Type: research

Discovery of novel inhibitors of human phosphoglycerate dehydrogenase by activity-directed combinatorial chemical synthesis strategy
Bioorg Chem. 2021 Jul 8;115:105159. doi: 10.1016/j.bioorg.2021.105159. Online ahead of print.ABSTRACTSerine, the source of the one-carbon units essential for de novo purine and deoxythymidine synthesis plays a crucial role in the growth of cancer cells. Phosphoglycerate dehydrogenase (PHGDH) which catalyzes the first, rate-limiting step in de novo serine biosynthesis has become a promising target for the cancer treatment. Here we identified H-G6 as a potential PHGDH inhibitor from the screening of an in-house small molecule library based on the enzymatic assay. We adopted activity-directed combinatorial chemical synthesis ...
Source: Bioorganic Chemistry - July 23, 2021 Category: Chemistry Authors: Xia Zhou Yuping Tan Kun Gou Lei Tao Yuan Luo Yue Zhou Zeping Zuo Qingxiang Sun Youfu Luo Yinglan Zhao Source Type: research

Benzimidazole analogues as efficient arsenals in war against methicillin-resistance staphylococcus aureus (MRSA) and its SAR studies
Bioorg Chem. 2021 Jul 17;115:105175. doi: 10.1016/j.bioorg.2021.105175. Online ahead of print.ABSTRACTSmall molecule based inhibitors development is a growing field in medicinal chemistry. In recent years, different heterocyclic derivatives have been designed to counter the infections caused by multi-drug resistant bacteria. Indeed, small molecule inhibitors can be employed as an efficient antibacterial agents with different mechanism of action. Methicillin-resistant Staphylococcus aureus (MRSA) is becoming lethal to mankind due to easy transmission mode, rapid resistance development to existing antibiotics and affect diff...
Source: Bioorganic Chemistry - July 23, 2021 Category: Chemistry Authors: Gao-Feng Zha Habbanakuppe D Preetham Shobith Rangappa Kothanahally S Sharath Kumar Yarabahally R Girish Kadalipura P Rakesh Milad Ashrafizadeh Ali Zarrabi Kanchugarakoppal S Rangappa Source Type: research

Current development of sigma-2 receptor radioligands as potential tumor imaging agents
Bioorg Chem. 2021 Jul 13;115:105163. doi: 10.1016/j.bioorg.2021.105163. Online ahead of print.ABSTRACTSigma receptors are transmembrane proteins with two different subtypes: σ1 and σ2. Because of its overexpression in tumors, the σ2 receptor (σ2R) is a well-known biomarker for cancer cells. A large number of small-molecule ligands for the σ2Rs have been identified and tested for imaging the proliferative status of tumors using single photon emission computed tomography (SPECT) and positron emission tomography (PET). These small molecules include derivatives of bicyclic amines, indoles, cyclohe...
Source: Bioorganic Chemistry - July 21, 2021 Category: Chemistry Authors: Zahra Shaghaghi Maryam Alvandi Zahra Ghanbarimasir Soghra Farzipour Saeed Emami Source Type: research

Current development of sigma-2 receptor radioligands as potential tumor imaging agents
Bioorg Chem. 2021 Jul 13;115:105163. doi: 10.1016/j.bioorg.2021.105163. Online ahead of print.ABSTRACTSigma receptors are transmembrane proteins with two different subtypes: σ1 and σ2. Because of its overexpression in tumors, the σ2 receptor (σ2R) is a well-known biomarker for cancer cells. A large number of small-molecule ligands for the σ2Rs have been identified and tested for imaging the proliferative status of tumors using single photon emission computed tomography (SPECT) and positron emission tomography (PET). These small molecules include derivatives of bicyclic amines, indoles, cyclohe...
Source: Bioorganic Chemistry - July 21, 2021 Category: Chemistry Authors: Zahra Shaghaghi Maryam Alvandi Zahra Ghanbarimasir Soghra Farzipour Saeed Emami Source Type: research

Novel insights on the molecular mechanism of action of the anti-angiogenic pyrazolyl-urea GeGe-3 by functional proteomics
Bioorg Chem. 2021 Jul 14;115:105168. doi: 10.1016/j.bioorg.2021.105168. Online ahead of print.ABSTRACTIn recent years, 5-pyrazolyl-ureas have mostly been known for their attractive poly-pharmacological outline and, in particular, ethyl 1-(2-hydroxypentyl)-5-(3-(3-(trifluoromethyl) phenyl) ureido)-1H-pyrazole-4-carboxylate (named GeGe-3) has emerged as a capable anti-angiogenic compound. This paper examines its interactome by functional proteomics using a label-free mass spectrometry based platform, coupling Drug Affinity Responsive Target Stability and targeted Limited Proteolysis-Multiple Reaction Monitoring. Calreticulin...
Source: Bioorganic Chemistry - July 20, 2021 Category: Chemistry Authors: Elva Morretta Raffaella Belvedere Antonello Petrella Andrea Spallarossa Federica Rapetti Olga Bruno Chiara Brullo Maria Chiara Monti Source Type: research

Novel insights on the molecular mechanism of action of the anti-angiogenic pyrazolyl-urea GeGe-3 by functional proteomics
Bioorg Chem. 2021 Jul 14;115:105168. doi: 10.1016/j.bioorg.2021.105168. Online ahead of print.ABSTRACTIn recent years, 5-pyrazolyl-ureas have mostly been known for their attractive poly-pharmacological outline and, in particular, ethyl 1-(2-hydroxypentyl)-5-(3-(3-(trifluoromethyl) phenyl) ureido)-1H-pyrazole-4-carboxylate (named GeGe-3) has emerged as a capable anti-angiogenic compound. This paper examines its interactome by functional proteomics using a label-free mass spectrometry based platform, coupling Drug Affinity Responsive Target Stability and targeted Limited Proteolysis-Multiple Reaction Monitoring. Calreticulin...
Source: Bioorganic Chemistry - July 20, 2021 Category: Chemistry Authors: Elva Morretta Raffaella Belvedere Antonello Petrella Andrea Spallarossa Federica Rapetti Olga Bruno Chiara Brullo Maria Chiara Monti Source Type: research

Pharmacophore-based drug design of AChE and BChE dual inhibitors as potential anti-Alzheimer's disease agents
Bioorg Chem. 2021 Jul 7;114:105149. doi: 10.1016/j.bioorg.2021.105149. Online ahead of print.ABSTRACTFor the Alzheimer's disease (AD) with complex pathogenesis, single target drugs represent one of the most effective therapeutic strategies in clinical. However, the traditional concept of "a disease, a target" is difficult to find very effective drugs, and multi-target drugs have already become new hot spot in drug development for this disease. In our present study, our efforts toward discovering new cholinesterase (ChE) inhibitors aided by computational methods will provide useful information as anti-AD agents in...
Source: Bioorganic Chemistry - July 12, 2021 Category: Chemistry Authors: Hongwei Gao Yingying Jiang Jiuyu Zhan Yingni Sun Source Type: research

Apoptotic effect of chromanone derivative, hyrtiosone A from marine demosponge Hyrtios erectus in hepatocellular carcinoma HepG2 cells
Bioorg Chem. 2021 Jun 24;114:105119. doi: 10.1016/j.bioorg.2021.105119. Online ahead of print.ABSTRACTThe tumor suppressor proteins p53 and p27 exhibited a significant role in the survival of cells and regulation of cellular division and growth. In majority of the human tumors, particularly in hepatocellular carcinoma, these proteins are inactivated by mutation or deletion, and are considered to predict the pathophysiology related to liver cancer. The present study evaluated the activation of the p53 and p27 pathways as a useful therapeutic tool to attenuate hepatocellular carcinoma. Three undescribed homologous chromanone...
Source: Bioorganic Chemistry - July 12, 2021 Category: Chemistry Authors: Kajal Chakraborty Prima Francis Source Type: research

Pharmacophore-based drug design of AChE and BChE dual inhibitors as potential anti-Alzheimer's disease agents
Bioorg Chem. 2021 Jul 7;114:105149. doi: 10.1016/j.bioorg.2021.105149. Online ahead of print.ABSTRACTFor the Alzheimer's disease (AD) with complex pathogenesis, single target drugs represent one of the most effective therapeutic strategies in clinical. However, the traditional concept of "a disease, a target" is difficult to find very effective drugs, and multi-target drugs have already become new hot spot in drug development for this disease. In our present study, our efforts toward discovering new cholinesterase (ChE) inhibitors aided by computational methods will provide useful information as anti-AD agents in...
Source: Bioorganic Chemistry - July 12, 2021 Category: Chemistry Authors: Hongwei Gao Yingying Jiang Jiuyu Zhan Yingni Sun Source Type: research

Apoptotic effect of chromanone derivative, hyrtiosone A from marine demosponge Hyrtios erectus in hepatocellular carcinoma HepG2 cells
Bioorg Chem. 2021 Jun 24;114:105119. doi: 10.1016/j.bioorg.2021.105119. Online ahead of print.ABSTRACTThe tumor suppressor proteins p53 and p27 exhibited a significant role in the survival of cells and regulation of cellular division and growth. In majority of the human tumors, particularly in hepatocellular carcinoma, these proteins are inactivated by mutation or deletion, and are considered to predict the pathophysiology related to liver cancer. The present study evaluated the activation of the p53 and p27 pathways as a useful therapeutic tool to attenuate hepatocellular carcinoma. Three undescribed homologous chromanone...
Source: Bioorganic Chemistry - July 12, 2021 Category: Chemistry Authors: Kajal Chakraborty Prima Francis Source Type: research

Pharmacophore-based drug design of AChE and BChE dual inhibitors as potential anti-Alzheimer's disease agents
Bioorg Chem. 2021 Jul 7;114:105149. doi: 10.1016/j.bioorg.2021.105149. Online ahead of print.ABSTRACTFor the Alzheimer's disease (AD) with complex pathogenesis, single target drugs represent one of the most effective therapeutic strategies in clinical. However, the traditional concept of "a disease, a target" is difficult to find very effective drugs, and multi-target drugs have already become new hot spot in drug development for this disease. In our present study, our efforts toward discovering new cholinesterase (ChE) inhibitors aided by computational methods will provide useful information as anti-AD agents in...
Source: Bioorganic Chemistry - July 12, 2021 Category: Chemistry Authors: Hongwei Gao Yingying Jiang Jiuyu Zhan Yingni Sun Source Type: research

Apoptotic effect of chromanone derivative, hyrtiosone A from marine demosponge Hyrtios erectus in hepatocellular carcinoma HepG2 cells
Bioorg Chem. 2021 Jun 24;114:105119. doi: 10.1016/j.bioorg.2021.105119. Online ahead of print.ABSTRACTThe tumor suppressor proteins p53 and p27 exhibited a significant role in the survival of cells and regulation of cellular division and growth. In majority of the human tumors, particularly in hepatocellular carcinoma, these proteins are inactivated by mutation or deletion, and are considered to predict the pathophysiology related to liver cancer. The present study evaluated the activation of the p53 and p27 pathways as a useful therapeutic tool to attenuate hepatocellular carcinoma. Three undescribed homologous chromanone...
Source: Bioorganic Chemistry - July 12, 2021 Category: Chemistry Authors: Kajal Chakraborty Prima Francis Source Type: research

Pharmacophore-based drug design of AChE and BChE dual inhibitors as potential anti-Alzheimer's disease agents
Bioorg Chem. 2021 Jul 7;114:105149. doi: 10.1016/j.bioorg.2021.105149. Online ahead of print.ABSTRACTFor the Alzheimer's disease (AD) with complex pathogenesis, single target drugs represent one of the most effective therapeutic strategies in clinical. However, the traditional concept of "a disease, a target" is difficult to find very effective drugs, and multi-target drugs have already become new hot spot in drug development for this disease. In our present study, our efforts toward discovering new cholinesterase (ChE) inhibitors aided by computational methods will provide useful information as anti-AD agents in...
Source: Bioorganic Chemistry - July 12, 2021 Category: Chemistry Authors: Hongwei Gao Yingying Jiang Jiuyu Zhan Yingni Sun Source Type: research

Apoptotic effect of chromanone derivative, hyrtiosone A from marine demosponge Hyrtios erectus in hepatocellular carcinoma HepG2 cells
Bioorg Chem. 2021 Jun 24;114:105119. doi: 10.1016/j.bioorg.2021.105119. Online ahead of print.ABSTRACTThe tumor suppressor proteins p53 and p27 exhibited a significant role in the survival of cells and regulation of cellular division and growth. In majority of the human tumors, particularly in hepatocellular carcinoma, these proteins are inactivated by mutation or deletion, and are considered to predict the pathophysiology related to liver cancer. The present study evaluated the activation of the p53 and p27 pathways as a useful therapeutic tool to attenuate hepatocellular carcinoma. Three undescribed homologous chromanone...
Source: Bioorganic Chemistry - July 12, 2021 Category: Chemistry Authors: Kajal Chakraborty Prima Francis Source Type: research

Pharmacophore-based drug design of AChE and BChE dual inhibitors as potential anti-Alzheimer's disease agents
Bioorg Chem. 2021 Jul 7;114:105149. doi: 10.1016/j.bioorg.2021.105149. Online ahead of print.ABSTRACTFor the Alzheimer's disease (AD) with complex pathogenesis, single target drugs represent one of the most effective therapeutic strategies in clinical. However, the traditional concept of "a disease, a target" is difficult to find very effective drugs, and multi-target drugs have already become new hot spot in drug development for this disease. In our present study, our efforts toward discovering new cholinesterase (ChE) inhibitors aided by computational methods will provide useful information as anti-AD agents in...
Source: Bioorganic Chemistry - July 12, 2021 Category: Chemistry Authors: Hongwei Gao Yingying Jiang Jiuyu Zhan Yingni Sun Source Type: research

Apoptotic effect of chromanone derivative, hyrtiosone A from marine demosponge Hyrtios erectus in hepatocellular carcinoma HepG2 cells
Bioorg Chem. 2021 Jun 24;114:105119. doi: 10.1016/j.bioorg.2021.105119. Online ahead of print.ABSTRACTThe tumor suppressor proteins p53 and p27 exhibited a significant role in the survival of cells and regulation of cellular division and growth. In majority of the human tumors, particularly in hepatocellular carcinoma, these proteins are inactivated by mutation or deletion, and are considered to predict the pathophysiology related to liver cancer. The present study evaluated the activation of the p53 and p27 pathways as a useful therapeutic tool to attenuate hepatocellular carcinoma. Three undescribed homologous chromanone...
Source: Bioorganic Chemistry - July 12, 2021 Category: Chemistry Authors: Kajal Chakraborty Prima Francis Source Type: research

Pharmacophore-based drug design of AChE and BChE dual inhibitors as potential anti-Alzheimer's disease agents
Bioorg Chem. 2021 Jul 7;114:105149. doi: 10.1016/j.bioorg.2021.105149. Online ahead of print.ABSTRACTFor the Alzheimer's disease (AD) with complex pathogenesis, single target drugs represent one of the most effective therapeutic strategies in clinical. However, the traditional concept of "a disease, a target" is difficult to find very effective drugs, and multi-target drugs have already become new hot spot in drug development for this disease. In our present study, our efforts toward discovering new cholinesterase (ChE) inhibitors aided by computational methods will provide useful information as anti-AD agents in...
Source: Bioorganic Chemistry - July 12, 2021 Category: Chemistry Authors: Hongwei Gao Yingying Jiang Jiuyu Zhan Yingni Sun Source Type: research

Apoptotic effect of chromanone derivative, hyrtiosone A from marine demosponge Hyrtios erectus in hepatocellular carcinoma HepG2 cells
Bioorg Chem. 2021 Jun 24;114:105119. doi: 10.1016/j.bioorg.2021.105119. Online ahead of print.ABSTRACTThe tumor suppressor proteins p53 and p27 exhibited a significant role in the survival of cells and regulation of cellular division and growth. In majority of the human tumors, particularly in hepatocellular carcinoma, these proteins are inactivated by mutation or deletion, and are considered to predict the pathophysiology related to liver cancer. The present study evaluated the activation of the p53 and p27 pathways as a useful therapeutic tool to attenuate hepatocellular carcinoma. Three undescribed homologous chromanone...
Source: Bioorganic Chemistry - July 12, 2021 Category: Chemistry Authors: Kajal Chakraborty Prima Francis Source Type: research

Pharmacophore-based drug design of AChE and BChE dual inhibitors as potential anti-Alzheimer's disease agents
Bioorg Chem. 2021 Jul 7;114:105149. doi: 10.1016/j.bioorg.2021.105149. Online ahead of print.ABSTRACTFor the Alzheimer's disease (AD) with complex pathogenesis, single target drugs represent one of the most effective therapeutic strategies in clinical. However, the traditional concept of "a disease, a target" is difficult to find very effective drugs, and multi-target drugs have already become new hot spot in drug development for this disease. In our present study, our efforts toward discovering new cholinesterase (ChE) inhibitors aided by computational methods will provide useful information as anti-AD agents in...
Source: Bioorganic Chemistry - July 12, 2021 Category: Chemistry Authors: Hongwei Gao Yingying Jiang Jiuyu Zhan Yingni Sun Source Type: research

Apoptotic effect of chromanone derivative, hyrtiosone A from marine demosponge Hyrtios erectus in hepatocellular carcinoma HepG2 cells
Bioorg Chem. 2021 Jun 24;114:105119. doi: 10.1016/j.bioorg.2021.105119. Online ahead of print.ABSTRACTThe tumor suppressor proteins p53 and p27 exhibited a significant role in the survival of cells and regulation of cellular division and growth. In majority of the human tumors, particularly in hepatocellular carcinoma, these proteins are inactivated by mutation or deletion, and are considered to predict the pathophysiology related to liver cancer. The present study evaluated the activation of the p53 and p27 pathways as a useful therapeutic tool to attenuate hepatocellular carcinoma. Three undescribed homologous chromanone...
Source: Bioorganic Chemistry - July 12, 2021 Category: Chemistry Authors: Kajal Chakraborty Prima Francis Source Type: research

Pomegranate peel extract polyphenols attenuate the SARS-CoV-2 S-glycoprotein binding ability to ACE2 Receptor: In silico and in vitro studies
In this study, both in silico and in vitro methods were employed for evaluation of pomegranate peel extract (PoPEx), their major polyphenols, as well as their major metabolite urolithin A, to attenuate the contact of S-glycoprotein RBD and ACE2. Our results showed that PoPEx, punicalin, punicalagin and urolithin A exerted significant potential to block the S-glycoprotein-ACE2 contact. These in vitro results strongly confirm the in silico predictions and provide a valuable insight in the potential of pomegranate polyphenols for application in SARS-CoV-2 infection.PMID:34246969 | DOI:10.1016/j.bioorg.2021.105145 (Source: Bioorganic Chemistry)
Source: Bioorganic Chemistry - July 11, 2021 Category: Chemistry Authors: Relja Suru čić Maja Travar Miroslav Petkovi ć Biljana Tubi ć Milo š P Stojiljković Milkica Grabe ž Katarina Šavikin Gordana Zduni ć Ranko Škrbić Source Type: research

Pyrazoline derivatives as tubulin polymerization inhibitors with one hit for Vascular Endothelial Growth Factor Receptor 2 inhibition
Bioorg Chem. 2021 Jul 1;114:105134. doi: 10.1016/j.bioorg.2021.105134. Online ahead of print.ABSTRACTIn this work, to check the effect of the transposition of the rings in typical patterns, a series of pyrazoline derivatives 3a-3t bearing the characteristic 3,4,5-trimethoxy phenyl and thiophene moieties were synthesized and evaluated as tubulin polymerization inhibitors. Basically, as the concise output of our design, a majority of the synthesized compounds showed potency in inhibiting the tubulin polymerization. The top hit, 3q, exhibited potent anti-proliferation activity on cancer cell lines. It was comparable on tubuli...
Source: Bioorganic Chemistry - July 11, 2021 Category: Chemistry Authors: Bing Yang Jiahua Zhou Fa Wang Xiao-Wei Hu Yujun Shi Source Type: research

Design and synthesis of novel quinazolinone-pyrazole derivatives as potential α-glucosidase inhibitors: Structure-activity relationship, molecular modeling and kinetic study
In this study, a new series of quinazolinone-pyrazole hybrids were designed, synthesized and screened for their α-glucosidase inhibitory activity. The results of the in vitro screening indicated that all the molecular hybrids exhibited more inhibitory activity (IC50 values ranging from 60.5 ± 0.3 µM-186.6 ± 20 μM) in comparison to standard acarbose (IC50 = 750.0 ± 10.0 µM). Limited structure-activity relationship suggested that the variation in the inhibitory activities of the compounds affected by different substitutions on phenyl rings of diphenyl pyrazole moiety. The enzyme kine...
Source: Bioorganic Chemistry - July 11, 2021 Category: Chemistry Authors: Fateme Azimi Homa Azizian Mohammad Najafi Farshid Hassanzadeh Hojjat Sadeghi-Aliabadi Jahan B Ghasemi Mohammad Ali Faramarzi Somayeh Mojtabavi Bagher Larijani Lotfollah Saghaei Mohammad Mahdavi Source Type: research

Design, synthesis and pharmacological screening of novel renoprotective methionine-based peptidomimetics: Amelioration of cisplatin-induced nephrotoxicity
Bioorg Chem. 2021 Jun 17;114:105100. doi: 10.1016/j.bioorg.2021.105100. Online ahead of print.ABSTRACTCisplatin (CP) is an effective chemotherapeutic agent for treatment of various types of cancer, however efforts are needed to reduce its toxic side effect. Previous studies revealed promising effect of peptides in decreasing CP induced nephrotoxicity. Herein, novel Met-based peptidomimetics were synthesized using N-acylbenzotriazole as acylating agent in high yield. Evaluation of renoprotective effect of the synthesized targets on CP treated kidney cell line (LLC-PK1) revealed that pretreatment with 1/3 IC50 of targets II,...
Source: Bioorganic Chemistry - July 11, 2021 Category: Chemistry Authors: Khalid A Agha Tarek S Ibrahim Nehal M Elsherbiny Mohamed El-Sherbiny Eatedal H Abdel-Aal Zakaria K Abdel-Samii Nader E Abo-Dya Source Type: research