In vitro and in silico growth inhibitory, anti-ovarian & anti-lung carcinoma effects of 1, 5 diarylpenta-1, 4-dien-3-one as synthetically modified curcumin analogue. Issue 18 (19th October 2022)

• Record Type: Journal Article
• Authors: Chowrasia, Deepak; Jafri, Asif; Azad, Iqbal; Rais, Juhi; Sharma, Nisha; Khan, Fahad; Kumar, Ajay; Kumar, Sudhir; Arshad, Md
• Is Part Of: Journal of biomolecular structure & dynamics. Volume 40:Issue 18(2022)
• Page Start: 8569
• Page End: 8586
• Publication Date: 2022-10-19
• Subjects: Docking -- carcinoma -- PA-1 cells -- A549 cells -- MTT assay -- ROS generation -- apoptosis; Biomolecules -- Periodicals; Molecular structure -- Periodicals; Molecular Biology -- Periodicals; Biomechanics -- Periodicals; 572
• DOI: 10.1080/07391102.2021.1914166
• Languages: English
• ISSNs: 0739-1102

Abstract

Abstract: 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 1 H-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