Synthesis and Cellular Evaluation of Some Oxepino- and Pyranoxanthone Derivatives as Antitumor Agents: A Comparative Study

Abstract

A set of six hitherto unknown oxepinoxanthone derivatives has been prepared for cellular evaluation in view of the known and impressive anticancer potential of some pyranoxanthone derivatives. A set of three structurally similar pyranoxanthone derivatives has also been prepared for a direct comparison of biological activity associated with a change in ring size, from six to seven, if any. Evaluation of their anticancer properties was attempted in three different cancer cell lines, such as HPV, cervical cancer cell line HeLa, hormone-responsive breast cancer cell line MCF7, and lung cancer cell line A549, as many of the naturally occurring pyranoxanthones have shown effective activity against these cell lines. The oxepinoxanthone derivatives 15, 16, and 18 showed significant anticancer effects (selectivity index > 1–1.5), increasing reactive oxygen species generation, leading to apoptotic DNA laddering and nuclear blebbing. Though the pyran analogues 21 and 23 showed cytotoxicity in MCF7 and A549 cell lines, they also showed poor selectivity indices against breast cancer, cervical cancer, and lung cancer.