Benzothiazoles exhibit broad-spectrum antitumor activity: Their potency, structure–activity and structure–metabolism relationships

•The design and synthesis of an antitumor activity oriented benzothiazole sublibrary.•The evaluation of antiproliferative activity against a panel of 60 human cancer cell lines.•The evaluation of metabolic stability incubated in human liver microsome in vitro.•Compound 9p, showing higher potency and primarily metabolic stability, was identified.

An antitumor activity oriented benzothiazole sublibrary was constructed from a hit compound 3 via a five stepwise procedure. All target compounds were screened for their antitumor activity against 60 human cancer cell lines. Compounds 9p, 12d and 12i, showing higher potency than hit 3, were identified. Particularly, the compound 9p gave its average 50% growth inhibition (GI50) at 0.38 μM. Furthermore, incubation in human liver microsome primarily proved their metabolic stability in vitro. General structure–activity and structure–metabolism relationships were both summarized, which provides information on further strategically optimization.

Graphical abstractAn antitumor activity oriented benzothiazole sublibrary was designed and synthesized. Compound 9p, showing higher potency and primarily metabolic stability, was identified.Figure optionsDownload full-size imageDownload as PowerPoint slide