Steroid‐Thiazoline Conjugates as New Cytotoxic Agents: Synthesis, Bioevaluation, and In Silico Studies

ABSTRACT Steroids, commonly containing a distinct four rings carbon scaffold, are an important class of natural products with diverse biofunctions, which mainly include plant sterols, bile acids, cardiac glycosides, steroid saponins, steroid alkaloids, etc., and have aroused growing interest in the fields of bioorganic and pharmaceutical research. To facilitate the development of novel chemical entities with potential cytotoxic activity, a series of skeleton diversity–guided steroid‐thiazoline conjugates were designed and synthesized. All target compounds were evaluated for their in vitro inhibitory activity against human melanoma (A875) and hepatocellular carcinoma (Huh7) cell lines. The results showed that most of the newly synthesized compounds exhibited potent cytotoxic effects compared to 5‐fluorouracil (5‐FU). Furthermore, comprehensive structure‐activity relationship analyses, supported by inhibition data and in silico studies, revealed that the nature of the steroidal scaffold significantly influences biological activity.