Improved synthesis and application of an alkyne-functionalized isoprenoid analogue to study the prenylomes of motor neurons, astrocytes and their stem cell progenitors
Bioorg Chem. 2024 Apr 16;147:107365. doi: 10.1016/j.bioorg.2024.107365. Online ahead of print.ABSTRACTProtein prenylation is one example of a broad class of post-translational modifications where proteins are covalently linked to various hydrophobic moieties. To globally identify and monitor levels of all prenylated proteins in a cell simultaneously, our laboratory and others have developed chemical proteomic approaches that rely on the metabolic incorporation of isoprenoid analogues bearing bio-orthogonal functionality followed by enrichment and subsequent quantitative proteomic analysis. Here, several improvements in the...
Source: Bioorganic Chemistry - April 18, 2024 Category: Chemistry Authors: Kiall F Suazo Vartika Mishra Sanjay Maity Shelby A Auger Katarzyna Justyna Alexandru M Petre Linda Ottoboni Jessica Ongaro Stefania P Corti Francesco Lotti Serge Przedborski Mark D Distefano Source Type: research
Antioxidant aromatic compounds from Amomum villosum and target prediction of active ingredients
Bioorg Chem. 2024 Apr 16;147:107375. doi: 10.1016/j.bioorg.2024.107375. Online ahead of print.ABSTRACTThe dried fruit of Amomum villosum is an important spice and medicinal plant that has received great attention in recent years due to its high content of bioactive components and its potential for food additives and drug development. However, the stems and leaves of A. villosum are usually disposed of as waste. Based on the study of the fruits of A. villosum, we also systematically studied its stems and leaves. Fourteen aromatic compounds (1-14) were isolated and identified from A. villosum, including five new compounds (1...
Source: Bioorganic Chemistry - April 18, 2024 Category: Chemistry Authors: Junming Liang Yang Xu Jinxia Chen Zhiruo Zhang Hui Wang Kexin Liu Dejuan Sun Hua Li Lixia Chen Source Type: research
Discovery of novel thiophene-3-carboxamide derivatives as potential VEGFR-2 inhibitors with anti-angiogenic properties
This study reports a series of novel thiophene-3-carboxamide derivatives based on PAN-90806 as VEGFR-2 inhibitors, among which compound 14d exhibits excellent anti-proliferative activity against HCT116, MCF7, PC3, and A549 cell lines, and has effective VEGFR-2 inhibitory activity with an IC50 value of 191.1 nM. Additionally, CETSA results indicated that VEGFR-2 was a relevant target of compound 14d in the cell lines, and compound 14d could also inhibit VEGFR-2 protein phosphorylation in A549 cell line. Furthermore, compound 14d inhibited colony formation, cell migration, and HUVECs tube formation in a dose-dependent manner...
Source: Bioorganic Chemistry - April 16, 2024 Category: Chemistry Authors: Tai Li Jiawei Wang Limiao Feng Qi Zhou Qian Xie Yanni Shen Rongxin Ji Xiaoping Liu Yan Wang Chun Hu Source Type: research
Dual site reactivity of indole-3-Schiff bases with S/Se/Cl substituted ketenes for stereoselective C-4 substituted indole- β-lactams, biological evaluations, magic chloro effect and molecular docking studies
Bioorg Chem. 2024 Apr 14;147:107337. doi: 10.1016/j.bioorg.2024.107337. Online ahead of print.ABSTRACTA convenient methodology for C-4 indole-β-lactam hybrids with chloro, sulphur and seleno substitutions through dual site reactivity of indole-3-Schiff bases towards ketenes has been developed. The reaction proceeded in a stereospecific manner with the exclusive formation of trans-β-lactams assigned with respect to C3-H and C4-H. The synthesized novel β-lactams have been characterized with the help of elemental analysis (CHNS) and spectroscopic techniques viz.1H NMR, 13C NMR, DEPT 135, HSQC and IR. The trans configuratio...
Source: Bioorganic Chemistry - April 16, 2024 Category: Chemistry Authors: Kiran Sharma Pankaj Kumar Amita Sharma Shamsher S Bari Gaganpreet Bhullar Subhash C Sahoo Aman Bhalla Source Type: research
13-Oxyingenol-dodecanoate inhibits the growth of non-small cell lung cancer cells by targeting ULK1
Bioorg Chem. 2024 Apr 15;147:107367. doi: 10.1016/j.bioorg.2024.107367. Online ahead of print.ABSTRACTLung cancer is the leading cause of cancer deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancers. Euphorbia kansui yielded 13-oxyingenol-dodecanoate (13OD), an ingenane-type diterpenoid, which had a strong cytotoxic effect on NSCLC cells. The underlying mechanism and potential target, however, remained unknown. The study found that 13OD effectively inhibited the cell proliferation and colony formation of NSCLC cells (A549 and H460 cells), with less toxicity in normal human lung epithe...
Source: Bioorganic Chemistry - April 16, 2024 Category: Chemistry Authors: Xin-Ye Wang Yu-Jue Wang Bo-Wen Guo Zi-Lin Hou Gu-Xue Zhang Zheng Han Qingbo Liu Guo-Dong Yao Shao-Jiang Song Source Type: research
Discovery of novel thiophene-3-carboxamide derivatives as potential VEGFR-2 inhibitors with anti-angiogenic properties
This study reports a series of novel thiophene-3-carboxamide derivatives based on PAN-90806 as VEGFR-2 inhibitors, among which compound 14d exhibits excellent anti-proliferative activity against HCT116, MCF7, PC3, and A549 cell lines, and has effective VEGFR-2 inhibitory activity with an IC50 value of 191.1 nM. Additionally, CETSA results indicated that VEGFR-2 was a relevant target of compound 14d in the cell lines, and compound 14d could also inhibit VEGFR-2 protein phosphorylation in A549 cell line. Furthermore, compound 14d inhibited colony formation, cell migration, and HUVECs tube formation in a dose-dependent manner...
Source: Bioorganic Chemistry - April 16, 2024 Category: Chemistry Authors: Tai Li Jiawei Wang Limiao Feng Qi Zhou Qian Xie Yanni Shen Rongxin Ji Xiaoping Liu Yan Wang Chun Hu Source Type: research
Dual site reactivity of indole-3-Schiff bases with S/Se/Cl substituted ketenes for stereoselective C-4 substituted indole- β-lactams, biological evaluations, magic chloro effect and molecular docking studies
Bioorg Chem. 2024 Apr 14;147:107337. doi: 10.1016/j.bioorg.2024.107337. Online ahead of print.ABSTRACTA convenient methodology for C-4 indole-β-lactam hybrids with chloro, sulphur and seleno substitutions through dual site reactivity of indole-3-Schiff bases towards ketenes has been developed. The reaction proceeded in a stereospecific manner with the exclusive formation of trans-β-lactams assigned with respect to C3-H and C4-H. The synthesized novel β-lactams have been characterized with the help of elemental analysis (CHNS) and spectroscopic techniques viz.1H NMR, 13C NMR, DEPT 135, HSQC and IR. The trans configuratio...
Source: Bioorganic Chemistry - April 16, 2024 Category: Chemistry Authors: Kiran Sharma Pankaj Kumar Amita Sharma Shamsher S Bari Gaganpreet Bhullar Subhash C Sahoo Aman Bhalla Source Type: research
13-Oxyingenol-dodecanoate inhibits the growth of non-small cell lung cancer cells by targeting ULK1
Bioorg Chem. 2024 Apr 15;147:107367. doi: 10.1016/j.bioorg.2024.107367. Online ahead of print.ABSTRACTLung cancer is the leading cause of cancer deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancers. Euphorbia kansui yielded 13-oxyingenol-dodecanoate (13OD), an ingenane-type diterpenoid, which had a strong cytotoxic effect on NSCLC cells. The underlying mechanism and potential target, however, remained unknown. The study found that 13OD effectively inhibited the cell proliferation and colony formation of NSCLC cells (A549 and H460 cells), with less toxicity in normal human lung epithe...
Source: Bioorganic Chemistry - April 16, 2024 Category: Chemistry Authors: Xin-Ye Wang Yu-Jue Wang Bo-Wen Guo Zi-Lin Hou Gu-Xue Zhang Zheng Han Qingbo Liu Guo-Dong Yao Shao-Jiang Song Source Type: research
Design, synthesis, and biological evaluation of cathepsin B cleavage albumin-binding SN38 prodrug in breast cancer
Bioorg Chem. 2024 Apr 13;147:107370. doi: 10.1016/j.bioorg.2024.107370. Online ahead of print.ABSTRACTHere, we introduce a novel and effective approach utilizing a cathepsin B cleavage albumin-binding SN38 prodrug specifically designed for the treatment of metastatic breast cancer. Termed Mal-va-mac-SN38, our prodrug exhibits a unique ability to rapidly and covalently bind with endogenous albumin, resulting in the formation of HSA-va-mac-SN38. This prodrug demonstrates exceptional stability in human plasma. Importantly, HSA-va-mac-SN38 showcases an impressive enhancement in cellular uptake by 4T1 breast cancer cells, prima...
Source: Bioorganic Chemistry - April 15, 2024 Category: Chemistry Authors: Yingxin Lu Ying Huang Jiyu Jin Jiahui Yu Wei Lu Shulei Zhu Source Type: research
Design, synthesis, and biological evaluation of cathepsin B cleavage albumin-binding SN38 prodrug in breast cancer
Bioorg Chem. 2024 Apr 13;147:107370. doi: 10.1016/j.bioorg.2024.107370. Online ahead of print.ABSTRACTHere, we introduce a novel and effective approach utilizing a cathepsin B cleavage albumin-binding SN38 prodrug specifically designed for the treatment of metastatic breast cancer. Termed Mal-va-mac-SN38, our prodrug exhibits a unique ability to rapidly and covalently bind with endogenous albumin, resulting in the formation of HSA-va-mac-SN38. This prodrug demonstrates exceptional stability in human plasma. Importantly, HSA-va-mac-SN38 showcases an impressive enhancement in cellular uptake by 4T1 breast cancer cells, prima...
Source: Bioorganic Chemistry - April 15, 2024 Category: Chemistry Authors: Yingxin Lu Ying Huang Jiyu Jin Jiahui Yu Wei Lu Shulei Zhu Source Type: research
Peroxynitrite-activated fluorescent probe with two reaction triggers for pathological diagnosis and therapeutic evaluation of inflammation
Bioorg Chem. 2024 Apr 9;147:107362. doi: 10.1016/j.bioorg.2024.107362. Online ahead of print.ABSTRACTExcessive peroxynitrite (ONOO-) is closely related to the occurrence and progression of inflammation. Therefore, the development of an efficacious ONOO- activatable probe holds great potential for the early diagnosis of pathological inflammation, and the direct evaluation of the therapeutic efficacy of active protectants. In this work, a new ONOO--activated fluorescent probe (SZP) which greatly improved the specificity and sensitivity (LOD = 8.03 nM) with large Stokes shift (150 nm) through introducing two reaction triggers...
Source: Bioorganic Chemistry - April 14, 2024 Category: Chemistry Authors: Feiyan Liu Manman Li Weixia Li Yingjie Ren Mingliang Zhang Hui Zhang Pan Wang Yali Wu Kehan Wang Xiaoyan Wang Xiaofei Chen Jinfa Tang Source Type: research
Design, synthesis, docking, and antiviral evaluation of some novel pyrimidinone-based α-aminophosphonates as potent H1N1 and HCoV-229E inhibitors
Bioorg Chem. 2024 Apr 8;147:107353. doi: 10.1016/j.bioorg.2024.107353. Online ahead of print.ABSTRACTDialkyl/aryl aminophosphonates, 3a-g and 4a-e were synthesized using the LiClO4 catalyzed Kabachnic Fields-type reaction straightforwardly and efficiently. The synthesized phosphonates structures were characterized using elemental analyses, FT-IR, 1H NMR, 13C NMR, and MS spectroscopy. The new compounds were subjected to in-silico molecular docking simulations to evaluate their potential inhibition against Influenza A Neuraminidase and RNA-dependent RNA polymerase of human coronavirus 229E. Subsequently, the compounds were f...
Source: Bioorganic Chemistry - April 14, 2024 Category: Chemistry Authors: Hend A Hekal Omar M Hammad Nasser R El-Brollosy Maha M Salem Abdou K Allayeh Source Type: research
Synthesis, structural, multitargeted molecular docking analysis of anti-cancer, anti-tubercular, DNA interactions of benzotriazole based macrocyclic ligand
Bioorg Chem. 2024 Apr 9;147:107361. doi: 10.1016/j.bioorg.2024.107361. Online ahead of print.ABSTRACTBiologically important macromolecule 1, 1', 3, 3' Bis - [2,3,5,6-Tetramethyl-p-phenylenebis(methylene)] dibenzotriazlinium dibromide hydrate (BTD) was synthesized and characterized using FT-IR, NMR and single-crystal XRD (SCXRD). SCXRD revealed that the compound was crystallized as a monoclinic system and associated through weak intermolecular interactions like H-bonding and π- π stacking interactions. These weak intermolecular interactions in BTD were studied using Crystal Explorer and Gaussian. The calculated energies f...
Source: Bioorganic Chemistry - April 13, 2024 Category: Chemistry Authors: P Pon Matheswari J Ilavarasi Jeyamalar Ancy Iruthayaraj B Ravindran Durai Nayagam Source Type: research
Discovery of a new class of potent pyrrolo[3,4-c]quinoline-1,3-diones based inhibitors of human dihydroorotate dehydrogenase: Synthesis, pharmacological and toxicological evaluation
Bioorg Chem. 2024 Apr 9;147:107359. doi: 10.1016/j.bioorg.2024.107359. Online ahead of print.ABSTRACTTwenty N-substituted pyrrolo[3,4-c]quinoline-1,3-diones 3a-t were synthesized by a cyclization reaction of Pfitzinger's quinoline ester precursor with the selected aromatic, heteroaromatic and aliphatic amines. The structures of all derivatives were confirmed by IR, 1H NMR, 13C NMR and HRMS spectra, while their purity was determined using HPLC techniques. Almost all compounds were identified as a new class ofpotent inhibitors against hDHODH among which 3a and 3t were the most active ones with the same IC50 values of 0.11 μ...
Source: Bioorganic Chemistry - April 13, 2024 Category: Chemistry Authors: Marina G Dimitrijevi ć Cornelia Roschger Kevin Lang Andreas Zierer Milica G Paunovi ć Ana D Obradovi ć Milo š M Matić Marijana Pocrni ć Nives Gali ć Andrija Ćirić Milan D Joksovi ć Source Type: research
Synthesis, structural, multitargeted molecular docking analysis of anti-cancer, anti-tubercular, DNA interactions of benzotriazole based macrocyclic ligand
Bioorg Chem. 2024 Apr 9;147:107361. doi: 10.1016/j.bioorg.2024.107361. Online ahead of print.ABSTRACTBiologically important macromolecule 1, 1', 3, 3' Bis - [2,3,5,6-Tetramethyl-p-phenylenebis(methylene)] dibenzotriazlinium dibromide hydrate (BTD) was synthesized and characterized using FT-IR, NMR and single-crystal XRD (SCXRD). SCXRD revealed that the compound was crystallized as a monoclinic system and associated through weak intermolecular interactions like H-bonding and π- π stacking interactions. These weak intermolecular interactions in BTD were studied using Crystal Explorer and Gaussian. The calculated energies f...
Source: Bioorganic Chemistry - April 13, 2024 Category: Chemistry Authors: P Pon Matheswari J Ilavarasi Jeyamalar Ancy Iruthayaraj B Ravindran Durai Nayagam Source Type: research
