University Institute of Pharmacy, CSJM University, Kanpur, India.
Department of Zoology, Molecular Endocrinology Lab, University of Lucknow, Lucknow, India.
J Biomol Struct Dyn. 2022 Nov;40(18):8569-8586. doi: 10.1080/07391102.2021.1914166. Epub 2021 May 6.
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 H-NMR). anti-proliferative activity was tested 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 (IC 73 and 79.7 µM) against human ovarian carcinoma and human lung adenocarcinoma, respectively.Communicated by Ramaswamy H. Sarma.
合成的 1,5-二芳基戊-1,4-二烯-3-酮衍生物（化合物 1-6）作为合成姜黄素类似物，对人卵巢腺癌和肺腺癌细胞的潜在抗癌活性进行了测试。所有化合物的吸收、分布、代谢、排泄和毒性（ADMET/药代动力学）参数均通过 admetSAR 软件进行预测。利用 Molinspiration 和 ChemDraw 计算基于 Lipinski 规则和 Ghose 滤波器的药代动力学、药效学和生物活性评分特性。利用 AutoDock Vina 和 iGEMDOCK 对所有化合物进行了分子对接评价，针对三种最常见的人类抗癌靶点：表皮生长因子受体（EGFR）、热休克蛋白（Hsp90-α）和血管内皮生长因子受体-2（VEGFR2）。将所得结果与参考化合物 7 和药物 8-10（7：GO-035；8：喹唑啉；9：纳喹替尼和 10：核糖呋喃尿嘧啶酰胺）进行比较。结果表明，所有化合物都有可能通过平均-9.1 的结合能（BE）与配体-受体复合物的活性部位进行相互作用，接触深度<5.0 Å。所有化合物均表现出良好的口服生物利用度、生物活性评分，且无任何化合物被发现具有毒性。化合物 1-6 还通过物理性质和光谱技术（FT-IR 和 H-NMR）成功进行了特征描述。采用 MTT 法对人卵巢癌细胞（PA-1）和人肺腺癌细胞（A549）进行抗增殖活性测试，并进一步筛选核片段化和 ROS 生成等凋亡参数。化合物 4 对人卵巢腺癌和人肺腺癌细胞的增殖活性具有良好的剂量依赖性（IC 73 和 79.7 μM）。通讯作者为 Ramaswamy H. Sarma。
