Discovery of pseudolaric acid A as a new Hsp90 inhibitor uncovers its potential anticancer mechanism
Bioorg Chem. 2021 May 5;112:104963. doi: 10.1016/j.bioorg.2021.104963. Online ahead of print.ABSTRACTPseudolaric acid A (PAA), one of the main bioactive ingredients in traditional medicine Pseudolarix cortex, exhibits remarkable anticancer activities. Yet its mechanism of action and molecular target have not been investigated and remain unclear. In this work, mechanistic study showed that PAA induced cell cycle arrest at G2/M phase and promoted cell death through caspase-8/caspase-3 pathway, demonstrating potent antiproliferation and anticancer activities. PAA was discovered to be a new Hsp90 inhibitor and multiple biophys...
Source: Bioorganic Chemistry - May 15, 2021 Category: Chemistry Authors: Jiangxin Liu Xing-De Wu Wenyan Li Zaifeng Yuan Kun Yang Qin-Shi Zhao Source Type: research

Anti-inflammatory effect of luteolin is related to the changes in the gut microbiota and contributes to preventing the progression from simple steatosis to nonalcoholic steatohepatitis
Bioorg Chem. 2021 May 5;112:104966. doi: 10.1016/j.bioorg.2021.104966. Online ahead of print.ABSTRACTIncreasing intestinal barrier function is one of the basic methods to suppress inflammation in the progression from simple steatosis (SS) to nonalcoholic steatohepatitis (NASH). Luteolin exists widely in vegetables, fruits and natural herbs and has various biological activities, including benefits on nonalcoholic fatty liver disease (NAFLD). However, its regulatory effects on the gut microbiota and involvement in its biological activities remain to be investigated. We fed rats a high-fat diet containing 0.5% luteolin for 12...
Source: Bioorganic Chemistry - May 15, 2021 Category: Chemistry Authors: Wen-Long Sun Jing-Wen Yang Hao-Yue Dou Gu-Qing Li Xin-Yu Li Liang Shen Hong-Fang Ji Source Type: research

Design, synthesis, in vitro and in vivo evaluation against MRSA and molecular docking studies of novel pleuromutilin derivatives bearing 1, 3, 4-oxadiazole linker
Bioorg Chem. 2021 May 1;112:104956. doi: 10.1016/j.bioorg.2021.104956. Online ahead of print.ABSTRACTA class of pleuromutilin derivatives containing 1, 3, 4-oxadiazole were designed and synthesized as potential antibacterial agents against Methicillin-resistant staphylococcus aureus (MRSA). The ultrasound-assisted reaction was proposed as a green chemistry method to synthesize 1, 3, 4-oxadiazole derivatives (intermediates 85-110). Among these pleuromutilin derivatives, compound 133 was found to be the strongest antibacterial derivative against MRSA (MIC = 0.125 μg/mL). Furthermore, the result of the time-kill curves dis...
Source: Bioorganic Chemistry - May 15, 2021 Category: Chemistry Authors: Jie Liu Guang-Yu Zhang Zhe Zhang Bo Li Fei Chai Qi Wang Zi-Dan Zhou Ling-Ling Xu Shou-Kai Wang Zhen Jin You-Zhi Tang Source Type: research

Advancements in folate receptor targeting for anti-cancer therapy: A small molecule-drug conjugate approach
Bioorg Chem. 2021 Apr 27;112:104946. doi: 10.1016/j.bioorg.2021.104946. Online ahead of print.ABSTRACTTargeted delivery combined with controlled release of drugs has a crucial role in future of personalized medicine. The majority of cancer drugs are intended to interfere with one or more cellular events. Anticancer agents can also be toxic to healthy cells, as healthy cells may also need to proliferate and avoid apoptosis. The focus of this review covers the principles, advantages, drawbacks and summarize criteria that must be met for design of small molecule-drug conjugates (SMDCs) to achieve the desired therapeutic poten...
Source: Bioorganic Chemistry - May 14, 2021 Category: Chemistry Authors: Abhilash Rana Seema Bhatnagar Source Type: research

Advancements in folate receptor targeting for anti-cancer therapy: A small molecule-drug conjugate approach
Bioorg Chem. 2021 Apr 27;112:104946. doi: 10.1016/j.bioorg.2021.104946. Online ahead of print.ABSTRACTTargeted delivery combined with controlled release of drugs has a crucial role in future of personalized medicine. The majority of cancer drugs are intended to interfere with one or more cellular events. Anticancer agents can also be toxic to healthy cells, as healthy cells may also need to proliferate and avoid apoptosis. The focus of this review covers the principles, advantages, drawbacks and summarize criteria that must be met for design of small molecule-drug conjugates (SMDCs) to achieve the desired therapeutic poten...
Source: Bioorganic Chemistry - May 14, 2021 Category: Chemistry Authors: Abhilash Rana Seema Bhatnagar Source Type: research

Design, synthesis and anti-influenza virus activity of furan-substituted spirothiazolidinones
Bioorg Chem. 2021 Apr 30;112:104958. doi: 10.1016/j.bioorg.2021.104958. Online ahead of print.ABSTRACTA new series of N-(3-oxo-1-thia-4-azaspiro[4.5]decan-4-yl)carboxamides have been designed, synthesized and evaluated as antiviral agents. The compounds were prepared by condensation of 2-methylfuran-3-carbohydrazide, appropriate carbonyl compounds and sulfanyl acids. The new molecules were characterized by IR, 1H NMR, 13C NMR, mass spectrometry and elemental analysis. Six analogues proved to be active against influenza A/H3N2 virus, the two most protent analogues, 3c and 3d, having an EC50 value of about 1 µM. These ...
Source: Bioorganic Chemistry - May 12, 2021 Category: Chemistry Authors: Çağla Begüm Apaydın Merve Tansuyu Zafer Cesur Lieve Naesens F üsun Göktaş Source Type: research

Structure-based modification of pyrazolone derivatives to inhibit mTORC1 by targeting the leucyl-tRNA synthetase-RagD interaction
In this study, in silico physicochemical properties and metabolite analysis of BC-LI-0186 are used to investigate the addition of functional groups to improve solubility and microsomal stability. In vitro experiments demonstrated that 7b and 8a had improved chemical properties while still maintaining inhibitory activity against mTORC1. The results suggest a new strategy for the discovery of novel drug candidates and the treatment of diverse mTORC1-related diseases.PMID:33979735 | DOI:10.1016/j.bioorg.2021.104907 (Source: Bioorganic Chemistry)
Source: Bioorganic Chemistry - May 12, 2021 Category: Chemistry Authors: Jae Hyun Kim Kilsoo Jung Chulho Lee Doona Song Kibum Kim Hee Chan Yoo Seung Joon Park Jong Soon Kang Kyeong-Ryoon Lee Sunghoon Kim Jung Min Han Gyoonhee Han Source Type: research

Design, synthesis and anti-influenza virus activity of furan-substituted spirothiazolidinones
Bioorg Chem. 2021 Apr 30;112:104958. doi: 10.1016/j.bioorg.2021.104958. Online ahead of print.ABSTRACTA new series of N-(3-oxo-1-thia-4-azaspiro[4.5]decan-4-yl)carboxamides have been designed, synthesized and evaluated as antiviral agents. The compounds were prepared by condensation of 2-methylfuran-3-carbohydrazide, appropriate carbonyl compounds and sulfanyl acids. The new molecules were characterized by IR, 1H NMR, 13C NMR, mass spectrometry and elemental analysis. Six analogues proved to be active against influenza A/H3N2 virus, the two most protent analogues, 3c and 3d, having an EC50 value of about 1 µM. These ...
Source: Bioorganic Chemistry - May 12, 2021 Category: Chemistry Authors: Çağla Begüm Apaydın Merve Tansuyu Zafer Cesur Lieve Naesens F üsun Göktaş Source Type: research

Structure-based modification of pyrazolone derivatives to inhibit mTORC1 by targeting the leucyl-tRNA synthetase-RagD interaction
In this study, in silico physicochemical properties and metabolite analysis of BC-LI-0186 are used to investigate the addition of functional groups to improve solubility and microsomal stability. In vitro experiments demonstrated that 7b and 8a had improved chemical properties while still maintaining inhibitory activity against mTORC1. The results suggest a new strategy for the discovery of novel drug candidates and the treatment of diverse mTORC1-related diseases.PMID:33979735 | DOI:10.1016/j.bioorg.2021.104907 (Source: Bioorganic Chemistry)
Source: Bioorganic Chemistry - May 12, 2021 Category: Chemistry Authors: Jae Hyun Kim Kilsoo Jung Chulho Lee Doona Song Kibum Kim Hee Chan Yoo Seung Joon Park Jong Soon Kang Kyeong-Ryoon Lee Sunghoon Kim Jung Min Han Gyoonhee Han Source Type: research

Synthesis, molecular docking, and in silico ADMET studies of 4-benzyl-1-(2,4,6-trimethyl-benzyl)-piperidine: Potential Inhibitor of SARS-CoV2
Bioorg Chem. 2021 May 5;112:104967. doi: 10.1016/j.bioorg.2021.104967. Online ahead of print.ABSTRACTNowadays, over 200 countries face a wellbeing emergency because of epidemiological disease COVID-19 caused by the SARS-CoV-2 virus. It will cause a very high effect on the world's economy and the worldwide health sector. The present work is an investigation of the newly synthesized 4-benzyl-1-(2,4,6-trimethyl-benzyl)-piperidine (M1BZP) molecule's inhibitory potential against important protein targets of SARS-CoV-2 using computational approaches. M1BZP crystallizes in monoclinic type with P1211 space group. For the title com...
Source: Bioorganic Chemistry - May 11, 2021 Category: Chemistry Authors: R Nandini Asha B Ravindran Durai Nayagam Nattamai Bhuvanesh Source Type: research

Synthesis, molecular docking, and in silico ADMET studies of 4-benzyl-1-(2,4,6-trimethyl-benzyl)-piperidine: Potential Inhibitor of SARS-CoV2
Bioorg Chem. 2021 May 5;112:104967. doi: 10.1016/j.bioorg.2021.104967. Online ahead of print.ABSTRACTNowadays, over 200 countries face a wellbeing emergency because of epidemiological disease COVID-19 caused by the SARS-CoV-2 virus. It will cause a very high effect on the world's economy and the worldwide health sector. The present work is an investigation of the newly synthesized 4-benzyl-1-(2,4,6-trimethyl-benzyl)-piperidine (M1BZP) molecule's inhibitory potential against important protein targets of SARS-CoV-2 using computational approaches. M1BZP crystallizes in monoclinic type with P1211 space group. For the title com...
Source: Bioorganic Chemistry - May 11, 2021 Category: Chemistry Authors: R Nandini Asha B Ravindran Durai Nayagam Nattamai Bhuvanesh Source Type: research

Bioconversion of antifungal viridin to phytotoxin viridiol by environmental non-viridin producing microorganisms
Bioorg Chem. 2021 May 1;112:104959. doi: 10.1016/j.bioorg.2021.104959. Online ahead of print.ABSTRACTBiotransformation of viridin, an antifungal produced by biocontrol agent, with non-viridin producing microorganisms is studied. The results show that some environmental non-targeted microorganisms are able to reduce it in the known phytotoxin viridiol, and its 3-epimer. Consequently, this reduction, which happens in some cases by detoxification mechanism, could be disastrous for the plant in a biocontrol of plant disease. However, a process fermentation/biotransformation could be an efficient approach for the preparation of...
Source: Bioorganic Chemistry - May 10, 2021 Category: Chemistry Authors: Gilles-Alex Pakora St éphane Mann Daouda Kone Didier Buisson Source Type: research

1,2,3-Triazole tethered 1,2,4 ‑trioxane trimer induces apoptosis in metastatic cancer cells and inhibits their proliferation, migration and invasion
Bioorg Chem. 2021 Apr 29;112:104952. doi: 10.1016/j.bioorg.2021.104952. Online ahead of print.ABSTRACTArtemisinin (ART) has been in use against different cancer cells and its derivatives and conjugates are more cytotoxic to iron-rich cancer cells. It is desirable to develop easily achievable synthetic 1,2,4-trioxanes having the same pharmacophore as that of ART. To explore more efficient compounds, a 1,2,3-triazole tethered 1,2,4‑trioxane trimer (4T) was synthesized and the anti-cancer effects of ART and 4T on MDA-MB-435 and MDA-MB-231 cells were investigated concerning regulation of osteopontin (OPN) expression, which i...
Source: Bioorganic Chemistry - May 10, 2021 Category: Chemistry Authors: Kitboklang Khongsti Bala Gangadhar Pasupuleti Bidyadhar Das Ghanashyam Bez Source Type: research

Bioconversion of antifungal viridin to phytotoxin viridiol by environmental non-viridin producing microorganisms
Bioorg Chem. 2021 May 1;112:104959. doi: 10.1016/j.bioorg.2021.104959. Online ahead of print.ABSTRACTBiotransformation of viridin, an antifungal produced by biocontrol agent, with non-viridin producing microorganisms is studied. The results show that some environmental non-targeted microorganisms are able to reduce it in the known phytotoxin viridiol, and its 3-epimer. Consequently, this reduction, which happens in some cases by detoxification mechanism, could be disastrous for the plant in a biocontrol of plant disease. However, a process fermentation/biotransformation could be an efficient approach for the preparation of...
Source: Bioorganic Chemistry - May 10, 2021 Category: Chemistry Authors: Gilles-Alex Pakora St éphane Mann Daouda Kone Didier Buisson Source Type: research

1,2,3-Triazole tethered 1,2,4 ‑trioxane trimer induces apoptosis in metastatic cancer cells and inhibits their proliferation, migration and invasion
Bioorg Chem. 2021 Apr 29;112:104952. doi: 10.1016/j.bioorg.2021.104952. Online ahead of print.ABSTRACTArtemisinin (ART) has been in use against different cancer cells and its derivatives and conjugates are more cytotoxic to iron-rich cancer cells. It is desirable to develop easily achievable synthetic 1,2,4-trioxanes having the same pharmacophore as that of ART. To explore more efficient compounds, a 1,2,3-triazole tethered 1,2,4‑trioxane trimer (4T) was synthesized and the anti-cancer effects of ART and 4T on MDA-MB-435 and MDA-MB-231 cells were investigated concerning regulation of osteopontin (OPN) expression, which i...
Source: Bioorganic Chemistry - May 10, 2021 Category: Chemistry Authors: Kitboklang Khongsti Bala Gangadhar Pasupuleti Bidyadhar Das Ghanashyam Bez Source Type: research

A study on MAPK/ERK and CDK2-Cyclin-E signal switch "on and off" in cell proliferation by bis urea derivatives of 1, 4-Diisocyanatobenzene
Bioorg Chem. 2021 Apr 23;112:104940. doi: 10.1016/j.bioorg.2021.104940. Online ahead of print.ABSTRACTA series of novel substituted bisurea 1,4-Diisocyanatobenzene compounds were designed, synthesized and introduced as potent anticancer compounds and screened for their in vitro anti-proliferative activities in human cancer cell lines. The structures of all titled compounds were characterized using Fourier-transform infrared mass spectra, nuclear magnetic resonance spectroscopy, elemental analysis and evaluated their sustainability using biological experiments. A selected group of ten derivatives were apprised for their ant...
Source: Bioorganic Chemistry - May 9, 2021 Category: Chemistry Authors: Vadabingi Nagalakshmamma Mallepogu Venkataswamy Chiranjeevi Pasala Amineni Uma Maheswari Kedam Thyaga Raju Chamarthi Nagaraju Ponne V Chalapathi Source Type: research

Potential new targets and drugs related to histone modifications in glioma treatment
Bioorg Chem. 2021 Apr 24;112:104942. doi: 10.1016/j.bioorg.2021.104942. Online ahead of print.ABSTRACTGlioma accounts for 40-50% of craniocerebral tumors, whose outcome rarely improves after standard treatment. The development of new therapeutic targets for glioma treatment has important clinical significance. With the deepening of research on gliomas, recent researchers have found that the occurrence and development of gliomas is closely associated with histone modifications, including methylation, acetylation, phosphorylation, and ubiquitination. Additionally, evidence has confirmed the close relationship between histone...
Source: Bioorganic Chemistry - May 9, 2021 Category: Chemistry Authors: Xiuhong Wei Bolian Xiao Liying Wang Lanlan Zang Fengyuan Che Source Type: research

Synthesis, in silico, in vitro and in vivo evaluations of isatin aroylhydrazones as highly potent anticonvulsant agents
In this study, a series of new isatin aroylhydrazones (5a-e and 6a-e) was synthesized and evaluated for their anticonvulsant activities. The (Z)-configuration of compounds was confirmed by 1H NMR. In vivo studies using maximal electroshock (MES) and pentylenetetrazole (PTZ) models of epilepsy in mice revealed that while most of compounds had no effect on chemically-induced seizures at the higher dose of 100 mg/kg but showed significant protection against electrically-induced seizures at the lower dose of 5 mg/kg. Certainly, N-methyl analogs 6a and 6e were found to be the most effective compounds, displaying 100% protection...
Source: Bioorganic Chemistry - May 8, 2021 Category: Chemistry Authors: Saeed Emami Mehdi Valipour Fatemeh Kazemi Komishani Fatemehsadat Sadati-Ashrafi Maria Rasoulian Majid Ghasemian Mahmood Tajbakhsh Patrick Honarchian Masihi Aidin Shakiba Hamid Irannejad Nematollah Ahangar Source Type: research

Synthesis, DFT, and eco-friendly insecticidal activity of some N-heterocycles derived from 4-((2-oxo-1,2-dihydroquinolin-3-yl)methylene)-2-phenyloxazol-5(4H)-one
Bioorg Chem. 2021 Apr 26;112:104945. doi: 10.1016/j.bioorg.2021.104945. Online ahead of print.ABSTRACTA new series of nitrogen heterocycles encompassing a quinoline scaffold such as imidazolone, benzimidazole, triazinone, triazole, and thiazole derivatives was synthesized utilizing the readily obtainable building block synthon, 4-((2-oxo-1,2-dihydroquinolin-3-yl)methylene)-2-phenyloxazol-5(4H)-one (3). It was interesting that the fused heterocycle, pyranoquinoline derivative 15 was successfully synthesized by different routes of reactions. The synthesized compounds were evaluated for their insecticidal activity and compoun...
Source: Bioorganic Chemistry - May 8, 2021 Category: Chemistry Authors: Eman A Ghareeb Naglaa F H Mahmoud Eman A El-Bordany Eman A E El-Helw Source Type: research

Discovery of thieno[2,3-d]pyrimidine-based derivatives as potent VEGFR-2 kinase inhibitors and anti-cancer agents
Bioorg Chem. 2021 Apr 27;112:104947. doi: 10.1016/j.bioorg.2021.104947. Online ahead of print.ABSTRACTVascular endothelial growth factor-2 (VEGFR-2) is considered one of the most important factors in tumor angiogenesis, and consequently a number of anticancer therapeutics have been developed to inhibit VEGFR-2 signaling. Accordingly, eighteen derivatives of thieno[2,3-d]pyrimidines having structural characteristics similar to VEGFR-2 inhibitors were designed and synthesized. Anticancer activities of the new derivatives were assessed against three human cancer cell lines (HCT-116, HepG2, and MCF-7) using MTT. Sorafenib was ...
Source: Bioorganic Chemistry - May 8, 2021 Category: Chemistry Authors: Souad A El-Metwally Mohsen M Abou-El-Regal Ibrahim H Eissa Ahmed B M Mehany Hazem A Mahdy Hazem Elkady Alaa Elwan Eslam B Elkaeed Source Type: research

Synthesis, antimicrobial, anti-cancer and in silico studies of new urea derivatives
Bioorg Chem. 2021 Apr 29;112:104953. doi: 10.1016/j.bioorg.2021.104953. Online ahead of print.ABSTRACTThe reaction of an alkyl or aryl isocyanates with some primary amines in acetonitrile at room temperature afforded the corresponding alkyl- and aryl-urea derivatives. All the prepared urea compounds have been elucidated by FTIR, NMR, and elemental analysis. The compounds 1 and 3 were confirmed by single-crystal X-ray diffraction. The 4-tolylsulfonyl isocyanate reacted with the aryl amines 1, 2, 3, and 2,4-dichloroaniline to afford the corresponding sulfonylurea derivatives 5-8. Likewise, the reaction of the isocyanates wit...
Source: Bioorganic Chemistry - May 8, 2021 Category: Chemistry Authors: Farid M Sroor Abdelmageed M Othman Mohamed A Tantawy Karima F Mahrous Mostafa E El-Naggar Source Type: research

Synthesis, in silico, in vitro and in vivo evaluations of isatin aroylhydrazones as highly potent anticonvulsant agents
In this study, a series of new isatin aroylhydrazones (5a-e and 6a-e) was synthesized and evaluated for their anticonvulsant activities. The (Z)-configuration of compounds was confirmed by 1H NMR. In vivo studies using maximal electroshock (MES) and pentylenetetrazole (PTZ) models of epilepsy in mice revealed that while most of compounds had no effect on chemically-induced seizures at the higher dose of 100 mg/kg but showed significant protection against electrically-induced seizures at the lower dose of 5 mg/kg. Certainly, N-methyl analogs 6a and 6e were found to be the most effective compounds, displaying 100% protection...
Source: Bioorganic Chemistry - May 8, 2021 Category: Chemistry Authors: Saeed Emami Mehdi Valipour Fatemeh Kazemi Komishani Fatemehsadat Sadati-Ashrafi Maria Rasoulian Majid Ghasemian Mahmood Tajbakhsh Patrick Honarchian Masihi Aidin Shakiba Hamid Irannejad Nematollah Ahangar Source Type: research

Synthesis, DFT, and eco-friendly insecticidal activity of some N-heterocycles derived from 4-((2-oxo-1,2-dihydroquinolin-3-yl)methylene)-2-phenyloxazol-5(4H)-one
Bioorg Chem. 2021 Apr 26;112:104945. doi: 10.1016/j.bioorg.2021.104945. Online ahead of print.ABSTRACTA new series of nitrogen heterocycles encompassing a quinoline scaffold such as imidazolone, benzimidazole, triazinone, triazole, and thiazole derivatives was synthesized utilizing the readily obtainable building block synthon, 4-((2-oxo-1,2-dihydroquinolin-3-yl)methylene)-2-phenyloxazol-5(4H)-one (3). It was interesting that the fused heterocycle, pyranoquinoline derivative 15 was successfully synthesized by different routes of reactions. The synthesized compounds were evaluated for their insecticidal activity and compoun...
Source: Bioorganic Chemistry - May 8, 2021 Category: Chemistry Authors: Eman A Ghareeb Naglaa F H Mahmoud Eman A El-Bordany Eman A E El-Helw Source Type: research

Discovery of thieno[2,3-d]pyrimidine-based derivatives as potent VEGFR-2 kinase inhibitors and anti-cancer agents
Bioorg Chem. 2021 Apr 27;112:104947. doi: 10.1016/j.bioorg.2021.104947. Online ahead of print.ABSTRACTVascular endothelial growth factor-2 (VEGFR-2) is considered one of the most important factors in tumor angiogenesis, and consequently a number of anticancer therapeutics have been developed to inhibit VEGFR-2 signaling. Accordingly, eighteen derivatives of thieno[2,3-d]pyrimidines having structural characteristics similar to VEGFR-2 inhibitors were designed and synthesized. Anticancer activities of the new derivatives were assessed against three human cancer cell lines (HCT-116, HepG2, and MCF-7) using MTT. Sorafenib was ...
Source: Bioorganic Chemistry - May 8, 2021 Category: Chemistry Authors: Souad A El-Metwally Mohsen M Abou-El-Regal Ibrahim H Eissa Ahmed B M Mehany Hazem A Mahdy Hazem Elkady Alaa Elwan Eslam B Elkaeed Source Type: research

Synthesis, antimicrobial, anti-cancer and in silico studies of new urea derivatives
Bioorg Chem. 2021 Apr 29;112:104953. doi: 10.1016/j.bioorg.2021.104953. Online ahead of print.ABSTRACTThe reaction of an alkyl or aryl isocyanates with some primary amines in acetonitrile at room temperature afforded the corresponding alkyl- and aryl-urea derivatives. All the prepared urea compounds have been elucidated by FTIR, NMR, and elemental analysis. The compounds 1 and 3 were confirmed by single-crystal X-ray diffraction. The 4-tolylsulfonyl isocyanate reacted with the aryl amines 1, 2, 3, and 2,4-dichloroaniline to afford the corresponding sulfonylurea derivatives 5-8. Likewise, the reaction of the isocyanates wit...
Source: Bioorganic Chemistry - May 8, 2021 Category: Chemistry Authors: Farid M Sroor Abdelmageed M Othman Mohamed A Tantawy Karima F Mahrous Mostafa E El-Naggar Source Type: research

Diterpenoids from the seeds of Euphorbia lathyris and their anti-inflammatory activity
Bioorg Chem. 2021 Apr 26;112:104944. doi: 10.1016/j.bioorg.2021.104944. Online ahead of print.ABSTRACTTwelve previously undescribed diterpenoids, euplarisans A-L (1-12), including one premyrsinane and eleven lathyranes, along with ten known analogues 13-22 were isolated from the seeds of Euphorbia lathyris. Their chemical structures were delineated by spectroscopic analysis and single-crystal X-ray diffraction. Interestingly, both 5 and 6 possessed an unusual trans-gem-dimethylcyclopropane as structural features and compound 8 was elucidated as premyrsinane-type diterpenoid. Meanwhile, a plausible biogenetic pathway for co...
Source: Bioorganic Chemistry - May 7, 2021 Category: Chemistry Authors: Yali Wang Zhuorui Song Yuanyuan Guo Huiru Xie Zhen Zhang Dejuan Sun Hua Li Lixia Chen Source Type: research

( ±)-Gancochlearols J - N, renoprotective meroterpenoids from Ganoderma cochlear
Bioorg Chem. 2021 Apr 26;112:104950. doi: 10.1016/j.bioorg.2021.104950. Online ahead of print.ABSTRACTFive pairs of meroterpenoid enantiomers, (±)-gancochlearols J - N (1-5), were isolated from the fruiting bodies of Ganoderma cochlear. Their structures were elucidated on the basis of 1D and 2D NMR and HRESIMS data. The absolute configurations of gancochlearols J - M (1-4) were assigned by electronic circular dichroism (ECD) calculations. Biological evaluation showed that (-)-1 and (-)-2 could inhibit renal fibrosis in TGF-β1-induced rat kidney proximal tubular cells (NRK-52e).PMID:33962091 | DOI:10.1016/j.bioo...
Source: Bioorganic Chemistry - May 7, 2021 Category: Chemistry Authors: Xiao-Hui Meng Fu-Ying Qin Xiao-Ting Jiang Yu Li Yong-Xian Cheng Source Type: research

Diterpenoids from the seeds of Euphorbia lathyris and their anti-inflammatory activity
Bioorg Chem. 2021 Apr 26;112:104944. doi: 10.1016/j.bioorg.2021.104944. Online ahead of print.ABSTRACTTwelve previously undescribed diterpenoids, euplarisans A-L (1-12), including one premyrsinane and eleven lathyranes, along with ten known analogues 13-22 were isolated from the seeds of Euphorbia lathyris. Their chemical structures were delineated by spectroscopic analysis and single-crystal X-ray diffraction. Interestingly, both 5 and 6 possessed an unusual trans-gem-dimethylcyclopropane as structural features and compound 8 was elucidated as premyrsinane-type diterpenoid. Meanwhile, a plausible biogenetic pathway for co...
Source: Bioorganic Chemistry - May 7, 2021 Category: Chemistry Authors: Yali Wang Zhuorui Song Yuanyuan Guo Huiru Xie Zhen Zhang Dejuan Sun Hua Li Lixia Chen Source Type: research

( ±)-Gancochlearols J - N, renoprotective meroterpenoids from Ganoderma cochlear
Bioorg Chem. 2021 Apr 26;112:104950. doi: 10.1016/j.bioorg.2021.104950. Online ahead of print.ABSTRACTFive pairs of meroterpenoid enantiomers, (±)-gancochlearols J - N (1-5), were isolated from the fruiting bodies of Ganoderma cochlear. Their structures were elucidated on the basis of 1D and 2D NMR and HRESIMS data. The absolute configurations of gancochlearols J - M (1-4) were assigned by electronic circular dichroism (ECD) calculations. Biological evaluation showed that (-)-1 and (-)-2 could inhibit renal fibrosis in TGF-β1-induced rat kidney proximal tubular cells (NRK-52e).PMID:33962091 | DOI:10.1016/j.bioo...
Source: Bioorganic Chemistry - May 7, 2021 Category: Chemistry Authors: Xiao-Hui Meng Fu-Ying Qin Xiao-Ting Jiang Yu Li Yong-Xian Cheng Source Type: research

Dimeric clerodane diterpenoids and antiviral constituents of Dodonaea viscosa
Bioorg Chem. 2021 Apr 15;112:104916. doi: 10.1016/j.bioorg.2021.104916. Online ahead of print.ABSTRACTThree unprecedented dimeric clerodane diterpenoids, dodovisdimers A-C (1-3), along with six known clerodane monomers (4-9), were isolated from Dodonaea viscosa. Compounds 1-3 may be biosynthetically formed via an intermolecular Diels-Alder [4+2] cycloaddition between the coexisting monomers 4-7. The structures of these clerodanes were characterized by spectroscopic techniques, X-ray crystallographic study, and ECD calculations. Some isolates exerted antiviral effects on human influenza A virus (H3N2) in vitro.PMID:33957537...
Source: Bioorganic Chemistry - May 6, 2021 Category: Chemistry Authors: Xiao-Tong Zhao Chun Lei Jin-Qiu You Ting Zhao Mei-Hua Yu Xun-Long Shi Xiao Hu Ai-Jun Hou Source Type: research

Concise synthesis and biological evaluation of 2-Aryl-3-Anilinobenzo[b]thiophene derivatives as potent apoptosis-inducing agents
Bioorg Chem. 2021 Apr 20;112:104919. doi: 10.1016/j.bioorg.2021.104919. Online ahead of print.ABSTRACTMany clinically used agents active in cancer chemotherapy exert their activity through the induction of cell death (apoptosis) by targeting microtubules, altering protein function or inhibiting DNA synthesis. The benzo[b]thiophene scaffold holds a pivotal place as a pharmacophore for the development of anticancer agents, and, in addition, this scaffold has many pharmacological activities. We have developed a flexible method for the construction of a new series of 2-aryl-3-(3,4,5-trimethoxyanilino)-6-methoxybenzo[b]thiophen...
Source: Bioorganic Chemistry - May 6, 2021 Category: Chemistry Authors: Romeo Romagnoli Delia Preti Ernest Hamel Roberta Bortolozzi Giampietro Viola Andrea Brancale Salvatore Ferla Giampaolo Morciano Paolo Pinton Source Type: research

Bioactive naphthoquinones and triterpenoids from the fruiting bodies of Taiwanofungus salmoneus
Bioorg Chem. 2021 Apr 23;112:104939. doi: 10.1016/j.bioorg.2021.104939. Online ahead of print.ABSTRACTDrug resistance of cancer cells stands for the major problem of the treatment failure for chemotherapy or target therapy. Overexpression of efflux pumps leading to multidrug resistance (MDR) is still an important issue needed to be solved. In the present study, Taiwanofungus salmoneus was selected as the topic and eleven undescribed constituents including four naphthoquinones salmonones A-D (1-4) and seven triterpenoids salmoneatins A-G (5-11), along with one chromanone (12) and two benzenoids (13 and 14) reported from the...
Source: Bioorganic Chemistry - May 5, 2021 Category: Chemistry Authors: Kun-Ching Cheng Chin-Fu Chen Chin-Chuan Hung Sio-Hong Lam Hsin-Yi Hung Yue-Chiun Li Fu-An Chen Po-Chuen Shieh Ping-Chung Kuo Tian-Shung Wu Source Type: research

Bioactive naphthoquinones and triterpenoids from the fruiting bodies of Taiwanofungus salmoneus
Bioorg Chem. 2021 Apr 23;112:104939. doi: 10.1016/j.bioorg.2021.104939. Online ahead of print.ABSTRACTDrug resistance of cancer cells stands for the major problem of the treatment failure for chemotherapy or target therapy. Overexpression of efflux pumps leading to multidrug resistance (MDR) is still an important issue needed to be solved. In the present study, Taiwanofungus salmoneus was selected as the topic and eleven undescribed constituents including four naphthoquinones salmonones A-D (1-4) and seven triterpenoids salmoneatins A-G (5-11), along with one chromanone (12) and two benzenoids (13 and 14) reported from the...
Source: Bioorganic Chemistry - May 5, 2021 Category: Chemistry Authors: Kun-Ching Cheng Chin-Fu Chen Chin-Chuan Hung Sio-Hong Lam Hsin-Yi Hung Yue-Chiun Li Fu-An Chen Po-Chuen Shieh Ping-Chung Kuo Tian-Shung Wu Source Type: research

Design, synthesis, and evaluation of N-benzylpyrrolidine and 1,3,4-oxadiazole as multitargeted hybrids for the treatment of Alzheimer's disease
Bioorg Chem. 2021 Apr 17;111:104922. doi: 10.1016/j.bioorg.2021.104922. Online ahead of print.ABSTRACTNovel N-Benzylpyrrolidine hybrids were designed, synthesized, and tested against multiple in-vitro and in-vivo parameters. Among all the synthesized molecules, 8f and 12f showed extensive inhibition against beta-secretase-1 (hBACE-1), human acetylcholinesterase (hAChE) & human butyrylcholinesterase (hBuChE). These molecules are also endowed with significant AChE-peripheral anionic site (PAS) binding capability, blood-brain barrier permeability, potential disassembly of Aβ aggregates along with neuroprotection abil...
Source: Bioorganic Chemistry - May 4, 2021 Category: Chemistry Authors: Priyanka Kumari Choubey Avanish Tripathi Manish Kumar Tripathi Ankit Seth Sushant Kumar Shrivastava Source Type: research

Discovery of 5-(or 6)-benzoxazoles and oxazolo[4,5-b]pyridines as novel candidate antitumor agents targeting hTopo II α
Bioorg Chem. 2021 Apr 14;112:104913. doi: 10.1016/j.bioorg.2021.104913. Online ahead of print.ABSTRACTDiscovery of novel anticancer drugs which have low toxicity and high activity is very significant area in anticancer drug research and development. One of the important targets for cancer treatment research is topoisomerase enzymes. In order to make a contribution to this field, we have designed and synthesized some 5(or 6)-nitro-2-(substitutedphenyl)benzoxazole (1a-1r) and 2-(substitutedphenyl)oxazolo[4,5-b]pyridine (2a-2i) derivatives as novel candidate antitumor agents targeting human DNA topoisomerase enzymes (hTopo I ...
Source: Bioorganic Chemistry - May 4, 2021 Category: Chemistry Authors: Esin Karatas Egemen Foto Tugba Ertan-Bolelli Gozde Yalcin-Ozkat Serap Yilmaz Sanaz Ataei Fatma Zilifdar Ilkay Yildiz Source Type: research

Design, synthesis, and evaluation of N-benzylpyrrolidine and 1,3,4-oxadiazole as multitargeted hybrids for the treatment of Alzheimer's disease
Bioorg Chem. 2021 Apr 17;111:104922. doi: 10.1016/j.bioorg.2021.104922. Online ahead of print.ABSTRACTNovel N-Benzylpyrrolidine hybrids were designed, synthesized, and tested against multiple in-vitro and in-vivo parameters. Among all the synthesized molecules, 8f and 12f showed extensive inhibition against beta-secretase-1 (hBACE-1), human acetylcholinesterase (hAChE) & human butyrylcholinesterase (hBuChE). These molecules are also endowed with significant AChE-peripheral anionic site (PAS) binding capability, blood-brain barrier permeability, potential disassembly of Aβ aggregates along with neuroprotection abil...
Source: Bioorganic Chemistry - May 4, 2021 Category: Chemistry Authors: Priyanka Kumari Choubey Avanish Tripathi Manish Kumar Tripathi Ankit Seth Sushant Kumar Shrivastava Source Type: research

Discovery of 5-(or 6)-benzoxazoles and oxazolo[4,5-b]pyridines as novel candidate antitumor agents targeting hTopo II α
Bioorg Chem. 2021 Apr 14;112:104913. doi: 10.1016/j.bioorg.2021.104913. Online ahead of print.ABSTRACTDiscovery of novel anticancer drugs which have low toxicity and high activity is very significant area in anticancer drug research and development. One of the important targets for cancer treatment research is topoisomerase enzymes. In order to make a contribution to this field, we have designed and synthesized some 5(or 6)-nitro-2-(substitutedphenyl)benzoxazole (1a-1r) and 2-(substitutedphenyl)oxazolo[4,5-b]pyridine (2a-2i) derivatives as novel candidate antitumor agents targeting human DNA topoisomerase enzymes (hTopo I ...
Source: Bioorganic Chemistry - May 4, 2021 Category: Chemistry Authors: Esin Karatas Egemen Foto Tugba Ertan-Bolelli Gozde Yalcin-Ozkat Serap Yilmaz Sanaz Ataei Fatma Zilifdar Ilkay Yildiz Source Type: research

Modified Oligonucleotides: New Structures, New Properties, and New Spheres of Application
Russ J Bioorg Chem. 2021;47(2):339-343. doi: 10.1134/S1068162021020175. Epub 2021 Apr 26.ABSTRACTNucleic acids have made a long and arduous journey "from the bench to the bedside." At present, it can be assumed that drugs based on modified oligonucleotides will find a worthy application in personalized medicine of the future.PMID:33935479 | PMC:PMC8074280 | DOI:10.1134/S1068162021020175 (Source: Bioorganic Chemistry)
Source: Bioorganic Chemistry - May 3, 2021 Category: Chemistry Authors: V G Metelev T S Oretskaya Source Type: research

Design, synthesis, and anticancer evaluation of novel andrographolide derivatives bearing an α,β-unsaturated ketone moiety
Bioorg Chem. 2021 Apr 24;112:104941. doi: 10.1016/j.bioorg.2021.104941. Online ahead of print.ABSTRACTA series of 1,2-didehydro-3-ox-andrographolide derivatives based on two Michael acceptors were designed, synthesized and evaluated for their anticancer activity against two human cancer cell lines (HCT116 and MCF-7). All tested compounds exhibited significant growth inhibitory effect on HCT116 and moderate to good inhibitory effect on MCF-7 cell proliferation. Compound 10b displayed the best inhibitory activities against both HCT116 and MCF-7 cell lines, with IC50 values of 2.49 and 7.80 μM respectively. Preliminary ant...
Source: Bioorganic Chemistry - May 3, 2021 Category: Chemistry Authors: Wei Cai Jieyi Li Cheng Chen Jiajia Wu Jiabin Li Xiaowen Xue Source Type: research

Discovery and development of tumor glycolysis rate-limiting enzyme inhibitors
Bioorg Chem. 2021 Apr 8;112:104891. doi: 10.1016/j.bioorg.2021.104891. Online ahead of print.ABSTRACTTumor cells mainly provide necessary energy and substances for rapid cell growth through aerobic perglycolysis rather than oxidative phosphorylation. This phenomenon is called the "Warburg effect". The mechanism of glycolysis in tumor cells is more complicated, which is caused by the comprehensive regulation of multiple factors. Abnormal enzyme metabolism is one of the main influencing factors and inhibiting the three main rate-limiting enzymes in glycolysis is thought to be important strategy for cancer treatment...
Source: Bioorganic Chemistry - May 3, 2021 Category: Chemistry Authors: Xueyan Sun Yijiao Peng Jingduo Zhao Zhizhong Xie Xiaoyong Lei Guotao Tang Source Type: research

Modified Oligonucleotides: New Structures, New Properties, and New Spheres of Application
Russ J Bioorg Chem. 2021;47(2):339-343. doi: 10.1134/S1068162021020175. Epub 2021 Apr 26.ABSTRACTNucleic acids have made a long and arduous journey "from the bench to the bedside." At present, it can be assumed that drugs based on modified oligonucleotides will find a worthy application in personalized medicine of the future.PMID:33935479 | PMC:PMC8074280 | DOI:10.1134/S1068162021020175 (Source: Bioorganic Chemistry)
Source: Bioorganic Chemistry - May 3, 2021 Category: Chemistry Authors: V G Metelev T S Oretskaya Source Type: research

Design, synthesis, and anticancer evaluation of novel andrographolide derivatives bearing an α,β-unsaturated ketone moiety
Bioorg Chem. 2021 Apr 24;112:104941. doi: 10.1016/j.bioorg.2021.104941. Online ahead of print.ABSTRACTA series of 1,2-didehydro-3-ox-andrographolide derivatives based on two Michael acceptors were designed, synthesized and evaluated for their anticancer activity against two human cancer cell lines (HCT116 and MCF-7). All tested compounds exhibited significant growth inhibitory effect on HCT116 and moderate to good inhibitory effect on MCF-7 cell proliferation. Compound 10b displayed the best inhibitory activities against both HCT116 and MCF-7 cell lines, with IC50 values of 2.49 and 7.80 μM respectively. Preliminary ant...
Source: Bioorganic Chemistry - May 3, 2021 Category: Chemistry Authors: Wei Cai Jieyi Li Cheng Chen Jiajia Wu Jiabin Li Xiaowen Xue Source Type: research

Discovery and development of tumor glycolysis rate-limiting enzyme inhibitors
Bioorg Chem. 2021 Apr 8;112:104891. doi: 10.1016/j.bioorg.2021.104891. Online ahead of print.ABSTRACTTumor cells mainly provide necessary energy and substances for rapid cell growth through aerobic perglycolysis rather than oxidative phosphorylation. This phenomenon is called the "Warburg effect". The mechanism of glycolysis in tumor cells is more complicated, which is caused by the comprehensive regulation of multiple factors. Abnormal enzyme metabolism is one of the main influencing factors and inhibiting the three main rate-limiting enzymes in glycolysis is thought to be important strategy for cancer treatment...
Source: Bioorganic Chemistry - May 3, 2021 Category: Chemistry Authors: Xueyan Sun Yijiao Peng Jingduo Zhao Zhizhong Xie Xiaoyong Lei Guotao Tang Source Type: research

Design, synthesis and biological evaluation of novel imidazole-chalcone derivatives as potential anticancer agents and tubulin polymerization inhibitors
Bioorg Chem. 2021 Apr 20;112:104904. doi: 10.1016/j.bioorg.2021.104904. Online ahead of print.ABSTRACTNovel imidazole-chalcone derivatives were designed and synthesized as tubulin polymerization inhibitors and anticancer agents. The antiproliferative activity of the imidazole-chalcone was assessed on some human cancer cell lines including A549 (adenocarcinoma human alveolar basal epithelial cells), MCF-7 (human breast cancer cells), MCF-7/MX (mitoxantrone resistant human breast cancer cells), and HEPG2 (human hepatocellular carcinoma cells). Generally, the imidazole-chalcone derivatives exhibited more cytotoxicity on A549 ...
Source: Bioorganic Chemistry - May 2, 2021 Category: Chemistry Authors: Sara Rahimzadeh Oskuei Salimeh Mirzaei Mohammad Reza Jafari-Nik Farzin Hadizadeh Farhad Eisvand Fatemeh Mosaffa Razieh Ghodsi Source Type: research

The mode of antibacterial action of quaternary N-benzylimidazole salts against emerging opportunistic pathogens
Bioorg Chem. 2021 Apr 23;112:104938. doi: 10.1016/j.bioorg.2021.104938. Online ahead of print.ABSTRACTQuaternary ammonium compounds (QACs) are antimicrobial agents displaying a broad spectrum of activity due to their mechanism of action targeting the bacterial membrane. The emergence of bacterial resistance to QACs, especially in times of pandemics, requires the continuous search for new and potent QACs structures. Here we report the synthesis and biological evaluation of QACs based on imidazole derivative, N-benzylimidazole. The antimicrobial activity was tested against a range of pathogenic bacteria and fungi, both ATCC ...
Source: Bioorganic Chemistry - May 2, 2021 Category: Chemistry Authors: Doris Crn čević Lucija Krce Linda Masteli ć Ana Maravi ć Barbara Soldo Ivica Aviani Ines Primo žič Renata Od žak Matilda Šprung Source Type: research

Identification of novel anti-inflammatory Nur77 modulators by virtual screening
Bioorg Chem. 2021 Apr 20;112:104912. doi: 10.1016/j.bioorg.2021.104912. Online ahead of print.ABSTRACTOrphan nuclear receptor Nur77 is a unique member of the NR4A nuclear receptor subfamily, which is critical for cellular processes especially the inflammatory responses. Many efforts have been made to discover novel scaffold small molecules targeting Nur77. Herein, we evaluated the previously reported binding sites in crystal structures of Nur77 with small molecules, and then discovered compound 13 as a hit of Nur77 via virtual screening targeting the best-scored binding site. Based on the results of fluorescence titration ...
Source: Bioorganic Chemistry - May 2, 2021 Category: Chemistry Authors: Xiaoyu Ding Zijie Zhao Yue Wu Hao Zhang Kaixian Chen Cheng Luo Xiaomin Luo Heng Xu Source Type: research

Molecular characteristics supporting l-Type amino acid transporter 1 (LAT1)-mediated translocation
Bioorg Chem. 2021 Apr 22;112:104921. doi: 10.1016/j.bioorg.2021.104921. Online ahead of print.ABSTRACTl-Type amino acid transporter 1 (LAT1) is an interesting protein due to its peculiar expression profile. It can be utilized not only as a carrier for improved or targeted drug delivery, e.g., into the brain but also as a target protein by which amino acid supply can be restricted, e.g., from the cancer cells. The recognition and binding processes of LAT1-ligands, such as amino acids and clinically used small molecules, including l-dopa, gabapentin, and melphalan, are today well-known. Binding to LAT1 is crucial, particular...
Source: Bioorganic Chemistry - May 2, 2021 Category: Chemistry Authors: Jussi K ärkkäinen Tuomo Laitinen Magdalena Markowicz-Piasecka Ahmed Montaser Marko Lehtonen Jarkko Rautio Mikko Gynther Antti Poso Kristiina M Huttunen Source Type: research

Bioactive monoterpene phenol dimers from the fruits of Psoralea corylifolia L
Bioorg Chem. 2021 Apr 20;112:104924. doi: 10.1016/j.bioorg.2021.104924. Online ahead of print.ABSTRACTNine undescribed monoterpene phenol dimers, bisbakuchiols D-L (1-9), were isolated from the fruits of Psoralea corylifolia L. Their structures were elucidated based on extensive spectral analysis. The absolute configurations of 1-9 were specified by experimental and quantum chemical calculations of ECD spectra, and that of 1 was further established by X-ray diffraction analysis using Cu Kα radiation. Bisbakuchiols (1-4) were composed of two bakuchiols, one of which was cyclized via a C-7'/ C-12' single bond to form a...
Source: Bioorganic Chemistry - May 2, 2021 Category: Chemistry Authors: Hu-Tong-Yue Gao Guang-Zhen Lang Ying-Da Zang Jie Ma Jing-Zhi Yang Fei Ye Jin-Ying Tian Pan-Pan Gao Chuang-Jun Li Dong-Ming Zhang Source Type: research

Design, microwave assisted synthesis, and molecular modeling study of some new 1,3,4-thiadiazole derivatives as potent anticancer agents and potential VEGFR-2 inhibitors
Bioorg Chem. 2021 Apr 17;112:104923. doi: 10.1016/j.bioorg.2021.104923. Online ahead of print.ABSTRACTA green and efficient method was developed for the synthesis of 1,3,4-thiadiazole based compounds under microwave (MW) activation. The nucleophile N-(5-amino-1,3,4-thiadiazol-2-yl)thiophene-2-carboxamide (3) was synthesized and reacted with different carbon electrophilic reagents to afford thiadiazolo-pyrimidine or imidazolo-thiadiazoline derivatives (4-6 and 8), respectively. Furthermore, a one-pot reaction of 3 with p-chlorobenzaldehyde and different carbon electrophile/ or nucleophiles under microwave irradiation yields...
Source: Bioorganic Chemistry - May 1, 2021 Category: Chemistry Authors: Saad R Atta-Allah Asmaa M AboulMagd Paula S Farag Source Type: research

Disaccharide-polyethylenimine organic nanoparticles as non-toxic in vitro gene transporters and their anticancer potential
Bioorg Chem. 2021 Apr 16;112:104918. doi: 10.1016/j.bioorg.2021.104918. Online ahead of print.ABSTRACTPolyethylenimines (PEIs) have been shown as efficient gene delivery vectors due to their unique properties, however, toxicity as well as non-specific interactions with the tissues/cells because of high charge density have hampered their use in clinical applications. To counter these concerns, here, we have prepared disachharide-PEI organic nanoparticles by mixing PEIs with non-reducing disaccharides, i.e. trehalose (TPONs) and sucrose (SPONs), under mild conditions. The fabricated nanoparticles were complexed with pDNA and...
Source: Bioorganic Chemistry - May 1, 2021 Category: Chemistry Authors: Reena Singh Pradeep Kumar Source Type: research