姜黄素
生物信息学
体外
抑制性突触后电位
卵巢癌
化学
癌症研究
药理学
肺
癌
医学
内科学
生物化学
卵巢癌
癌症
基因
作者
Deepak Chowrasia,Asif Jafri,Iqbal Azad,Juhi Rais,Nisha Sharma,Fahad Khan,Ajay Kumar,Sudhir Kumar,Mohammad Arshad
标识
DOI:10.1080/07391102.2021.1914166
摘要
The synthesized 1,5 diarylpenta-1,4-dien-3-one derivatives (compounds 1-6) as synthetic curcumin analogues were tested for their potential anticancer activity against human ovarian and lung adenocarcinoma cells. The absorption, distribution, metabolism, excretion, and toxicity (ADMET/pharmacokinetic) parameters of all the compounds were predicted by admetSAR software. The pharmacokinetics, pharmacodynamics and bioactivity scores properties based on Lipinski rule and Ghose filter, calculated with the help of Molinspiration and ChemDraw. Molecular docking evaluation of all the compounds was also performed by using AutoDock Vina and iGEMDOCK against three most common human anticancer targets; epidermal growth factor receptor (EGFR), heat shock protein (Hsp 90-α), and vascular endothelial growth factor receptor-2 (VEGFR2). The obtained results were compared with the reference compound 7 and drugs 8-10 (7: GO-035; 8: Quinazolin; 9: Naquotinib and 10: Ribofuranuronamide). Finding indicates, all the compounds were potentially interacting with VEGFR2 through the average –9.1 binding energy (BE) with closer contact <5.0 Å deep in the active site of the ligand-receptor complex. All the compounds showed excellent oral bioavailability, bioactivity score, and none of the compounds are virtually found to be toxic. Compounds 1-6 were also successfully characterized by the physical properties as well as spectroscopic techniques (FT-IR and 1H-NMR). In vitro anti-proliferative activity was tested via MTT method against human ovarian carcinoma (PA-1) and human lung adenocarcinoma (A549) cells and further screened for apoptotic parameters such as nuclear fragmentation and ROS generation. Compound 4 exhibits good dose-dependent anti-proliferative activity (IC50 73 and 79.7 µM) against human ovarian carcinoma and human lung adenocarcinoma, respectively.Communicated by Ramaswamy H. Sarma
科研通智能强力驱动
Strongly Powered by AbleSci AI