Novel Benzothiazole Benzimidazole and Benzoxazole Derivatives as Potential Antitumor Agents: Synthesis and Preliminary in Vitro Biological Evaluation

摘要

In a previous hit-to-lead research program targeting anticancer agents, two promising lead compounds, >1a and >1b, were found. However, the poor solubility of >1a and >1b made difficult further in vivo studies. To solve this problem, a lead optimization was conducted through introducing N-methyl-piperazine groups at the 2-position and 6-position. To our delight, the optimized analogue >1d showed comparable antiproliferative activity in vitro with better solubility, compared with >1a. Based on this result, the replacement of the benzothiazole scaffold with benzimidazole and benzoxazole moieties afforded >1f and >1g, whose activities were fundamentally retained. In the preliminary in vitro biological evaluation, the immunofluorescence staining of HCT116 cells indicated that >1d, >1f and >1g led to cytosolic vacuolization which was not induced by >1a at low micromolecular concentrations. These results suggest that these optimized compounds might potentially constitute a novel class of anticancer agents, which merit further studies.