Synthesis and biological evaluation of 4β-benzoxazolepodophyllotoxin hybrids as DNA topoisomerase-II targeting anticancer agents

Abstract

A series of new 4β-benzoxazolepodophyllotoxin compounds (9a–j) were prepared and screened for cytotoxicity against four human tumour cell lines (HeLa, DU-145, A-159 and MCF-7). Among these compounds, 9a, 9c, 9f and 9i have shown more potent anticancer activity than etoposide with considerable IC₅₀ values. Apoptosis evaluation studies were performed using the Hoechst-33258 staining method and it was found specially that the best active compound 9i shows clear nuclear damage compared to etoposide. Molecular docking studies were also carried out to recognize the interactions against DNA topoisomerase-II and it was found that the energy calculations were in good agreement with the observed IC₅₀ value.