Synthesis and biological activity, and molecular modelling studies of potent cytotoxic podophyllotoxin-naphthoquinone compounds
Ha Thanh Nguyen, Quynh Giang Nguyen Thi, Nguyễn Thị Thu Hà, Phượng Hoàng Thị, Le Nhat Thuy Giang, Tuyet Anh Dang Thi, Bao Le-Quang, Hai Pham‐The, Tuyen Van Nguyen
Abstract
A new approach for the synthesis of podophyllotoxin-naphthoquinone compounds using microwave-assisted three-component reactions is reported in this study. Novel podophyllotoxin-naphthoquinone derivatives with modification on ring E were synthesized. All the synthetic compounds were assessed in terms of their cytotoxicity profile against four cancer cell lines (KB, HepG2, A549, and MCF7), and noncancerous Hek-293 cell lines. Notably, treatment of SK-LU-1 cells with compounds 5a and 5b resulted in G2/M phase arrest of the cell cycle, caspase-3/7 activation, and apoptosis. Additionally, molecular docking studies were performed and showed important interaction of two compounds against residues in the colchicine-binding-site of tubulin as well. Taken together, compounds 5a and 5b were identified as potent anticancer agents.