Synthesis, molecular docking analysis and <i>in vitro</i> evaluation of new heterocyclic hybrids of 4-aza-podophyllotoxin as potent cytotoxic agents
Ha Thanh Nguyen, Ket Tran Van, Hai Pham‐The, Julien Braire, Phượng Hoàng Thị, Tuan Anh Nguyen, Quynh Giang Nguyen Thi, Tuyet Anh Dang Thi, Le Nhat Thuy Giang, Tu Anh Le Thi, Doan Vu Ngoc, Tuyen Van Nguyen
Abstract
values ranging from 0.23 to 0.27 μM, which were between 5- to 10-fold more potent than the positive control ellipticine. Compounds 13a (HetAr = thiophen-3-yl) and 13d (HetAr = 5-bromofuran-2-yl) displayed high cytotoxic selectivity for A549 and HepG2 cancer cell lines when compared to the other cancer cell lines and low toxicity to the normal Hek-293 cell line. Molecular docking study was conducted to evaluate the interaction of new synthesized compounds with the colchicine-binding-site of tubulin. Besides that, physicochemical and pharmacokinetic properties of the most active compounds 13h,k were predicted.