Exploring cyclopropylamine containing cyanopyrimidines as LSD1 inhibitors: Design, synthesis, ADMET, MD analysis and anticancer activity profiling
Bioorg Chem. 2024 Apr 16;147:107336. doi: 10.1016/j.bioorg.2024.107336. Online ahead of print.ABSTRACTIn this series we report the structure-based design, synthesis and anticancer activity evaluation of a series of eighteen cyclopropylamine containing cyanopyrimidine derivatives. The computational predictions of ADMET properties revealed appropriate aqueous solubility, high GI absorption, no BBB permeability, no Lipinski rule violations, medium total clearance and no mutagenic, tumorigenic, irritant and reproductive toxic risks for most of the compounds. Compounds VIIb, VIIi and VIIm emerged as the most potent anticancer a...
Source: Bioorganic Chemistry - April 18, 2024 Category: Chemistry Authors: Khursheed Ahmad Sheikh Darakhshan Parveen M Mumtaz Alam Faizul Azam Mohammad Ahmed Khan Mymoona Akhter Sharba Tasneem None Meenu Suhel Parvez Khalid Imtiyaz Moshahid A Rizvi M Shaquiquzzaman Source Type: research
Non-peptidic inhibitors targeting SARS-CoV-2 main protease: A review
Bioorg Chem. 2024 Apr 16;147:107380. doi: 10.1016/j.bioorg.2024.107380. Online ahead of print.ABSTRACTThe COVID-19 pandemic continues to pose a threat to global health, and sounds the alarm for research & development of effective anti-coronavirus drugs, which are crucial for the patients and urgently needed for the current epidemic and future crisis. The main protease (Mpro) stands as an essential enzyme in the maturation process of SARS-CoV-2, playing an irreplaceable role in regulating viral RNA replication and transcription. It has emerged as an ideal target for developing antiviral agents against SARS-CoV-2 due to ...
Source: Bioorganic Chemistry - April 18, 2024 Category: Chemistry Authors: Ya-Qi Xiao Jiao Long Shuang-Shuang Zhang Yuan-Yuan Zhu Shuang-Xi Gu Source Type: research
Inhibition of TGF- β1/Smad3 signaling by compound 5aa: A potential treatment for idiopathic pulmonary fibrosis
In this study, we conducted the design and synthesis of 23 new inhibitors that specifically target the TGF-β1/Smad3 pathway. Initially, we employed a cell model of TGF-β-induced pulmonary fibrosis, using cell survival rate and HYP expression as indicators to identify the potent ingredient 5aa, which demonstrated significant anti-pulmonary fibrosis activity. Subsequently, we induced mice with bleomycin (BLM) to establish an experimental animal model of pulmonary fibrosis, and evaluated the pharmacodynamics of 5aa in vivo against pulmonary fibrosis. The alterations in HYP and collagen levels in BLM-induced pulmonary fibros...
Source: Bioorganic Chemistry - April 18, 2024 Category: Chemistry Authors: Baijiao An Yanhua Fang Lihan Wang Wenyan Nie Mengxuan Wang Haoran Nie Chengjun Wu Ruoyu Wang Source Type: research
The novel small molecule E0924G dually regulates bone formation and bone resorption through activating the PPAR δ signaling pathway to prevent bone loss in ovariectomized rats and senile mice
In conclusion, these data strongly suggest that E0924G has the potential to prevent OVX-induced and age-related osteoporosis by dual regulation of bone formation and bone resorption through activation of the PPARδ signaling pathway.PMID:38636434 | DOI:10.1016/j.bioorg.2024.107364 (Source: Bioorganic Chemistry)
Source: Bioorganic Chemistry - April 18, 2024 Category: Chemistry Authors: Yining Li Chao Liu Xiaowan Han Ren Sheng Li Bao Lijuan Lei Yexiang Wu Quanjie Li Yuyan Zhang Jing Zhang Weizhi Wang Yuhao Zhang Shunwang Li Chenyin Wang Xinwei Wei Jingrui Wang Zonggen Peng Yanni Xu Shuyi Si Source Type: research
Effective α-glycosidase inhibitors based on polyphenolic benzothiazole heterocycles
Bioorg Chem. 2024 Apr 12;147:107366. doi: 10.1016/j.bioorg.2024.107366. Online ahead of print.ABSTRACTα-Glycosidase inhibition is one of the main approaches to treat Diabetes mellitus. Polyphenolic moieties are known to be responsible for yielding exhibit potent α-glycosidase inhibitory effects. In addition, compounds containing benzothiazole and Schiff base functionalities were previously reported to show α-glycosidase inhibition. In this paper, the synthesis of seven new phloroglucinol-containing benzothiazole Schiff base derivatives through the reaction of 6-substituted-2-aminobenzothiazole compounds with 2,4,6-trihy...
Source: Bioorganic Chemistry - April 18, 2024 Category: Chemistry Authors: Esra Sevimli G ökçe Seyhan Didem Akkaya Suat Sar ı Burak Barut Baybars K öksoy Source Type: research
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
