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 R(1) and R(4) substituents of the naphthyl moiety for the biological profile of the series.
Laboratoire de Pharmaco-Chimie Radicalaire, LPCR, CNRS-UMR 7273, Institut de Chimie Radicalaire, Faculté de Pharmacie, Aix-Marseille Univ, 27 Boulevard Jean Moulin-CS30064, 13385 Marseille cedex 05, France.
Anita
A
Cohen
Pierre
P
Verhaeghe
Maxime D
MD
Crozet
Sébastien
S
Hutter
Pascal
P
Rathelot
Patrice
P
Vanelle
Nadine
N
Azas
D000981:Antiprotozoal Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D060326:Chemistry Techniques, Synthetic; D056945:Hep G2 Cells; D006801:Humans; D010963:Plasmodium falciparum / Q000187:drug effects*; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity
D000981:Antiprotozoal Agents; D013844:Thiazoles