Tandem synthesis and in vitro antiplasmodial evaluation of new naphtho[2,1-d]thiazole derivatives

A series of naphtho[2,1-d]thiazoles was prepared in good yields under microwave irradiation with an original protocol combining tandem direct arylation and intramolecular Knoevenagel reaction on 1,3-thiazole derivatives. Antiplasmodial evaluation of this series highlighted two hit compounds (compounds 11 and 13) displaying promising in vitro activity on the multiresistant K1 Plasmodium falciparum strain. Structure-toxicity and structure–activity relationships are also discussed and reveal the importance of the R1 and R4 substituents of the naphthyl moiety for the biological profile of the series.

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► An original « one pot » synthesis of new naphtho[2,1-d]thiazoles is presented.
► The structures of the synthesized compounds are reported.
►  Two hit compounds display a promising in vitro antiplasmodial activity.
► R1 substituent plays a key role in cytotoxicity and antiplasmodial activity.
► R4 substituent is also important for the biological profile of the series.