期刊
MOLECULES
卷 28, 期 2, 页码 -出版社
MDPI
DOI: 10.3390/molecules28020540
关键词
aminoquinoline-benzimidazole hybrids; anticancer; in silico ADME; docking; cell cycle perturbation; mitochondrial membrane potential; apoptosis
New 7-chloro-4-aminoquinoline-benzimidazole compounds were synthesized and characterized. They showed strong cytotoxic activity and effectively suppressed cell cycle progression in leukemia and lymphoma cells. Compound 12d exhibited good solubility and permeability, bound to c-Src with high affinity, and could be a potential candidate for the development of antitumor drugs.
In this study, new 7-chloro-4-aminoquinoline-benzimidazole compounds were synthesized and characterized by NMR, MS, and elemental analysis. These novel hybrids differ in the type of linker and in the substituent on the benzimidazole moiety. Their antiproliferative activities were evaluated on one non-tumor (MDCK1) and seven selected tumor (CaCo-2, MCF-7, CCRF-CEM, Hut78, THP-1, and Raji) cell lines by MTT test and flow cytometry analysis. The compounds with different types of linkers and an unsubstituted benzimidazole ring, 5d, 8d, and 12d, showed strong cytotoxic activity (the GI(50) ranged from 0.4 to 8 mu M) and effectively suppressed the cell cycle progression in the leukemia and lymphoma cells. After 24 h of treatment, compounds 5d and 12d induced the disruption of the mitochondrial membrane potential as well as apoptosis in HuT78 cells. The drug-like properties and bioavailability of the compounds were calculated using the Swiss ADME web tool, and a molecular docking study was performed on tyrosine-protein kinase c-Src (PDB: 3G6H). Compound 12d showed good solubility and permeability and bound to c-Src with an energy of -119.99 kcal/mol, forming hydrogen bonds with Glu310 and Asp404 in the active site and other residues with van der Waals interactions. The results suggest that compound 12d could be a leading compound in the further design of effective antitumor drugs.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据