Discovery of Structural Diversity Guided N‐S Heterocyclic Derivatives Based on Natural Benzothiazole Alkaloids as Potential Cytotoxic Agents

ABSTRACT Benzothiazole alkaloids are a class of rare heterocyclic alkaloids with unique structures and exhibit a wide range of biological activities. So, the aim of this work is to investigate structural diversity‐guided N‐S heterocyclic derivatives based on natural benzothiazole alkaloids as potential cytotoxic agents. Three series of novel benzothiazole derivatives, including 22 compounds, were designed and synthesized using pharmacophore hybridization, and their in vitro cytotoxic activities against Huh‐7 and A875 were fully evaluated. The results indicated that some of these benzothiazole derivatives had significantly good cytotoxic activities against two tested cell lines compared with the positive control 5‐fluorouracil, and other compounds 3f–3i displayed good selectivity between A875 and Huh‐7 cell lines, which might be used as promising lead molecule for discovery of novel benzothiazole‐type cytotoxic agents.