A small library of antiplasmodial methoxy-​thiazinoquinones, rationally designed on the model of the previously identified hit 1, has been prepd. by a simple and inexpensive procedure. The synthetic derivs. have been subjected to in vitro pharmacol. screening, including antiplasmodial and toxicity assays. These studies afforded a new lead candidate, compd. 9, endowed with higher antiplasmodial potency compared to 1, a good selectivity index when tested against a panel of mammalian cells, no toxicity against RBCs, a synergistic antiplasmodial action in combination with dihydroartemisinin, and a promising inhibitory activity on stage V gametocyte growth. Computational studies provided useful insights into the structural requirements needed for the antiplasmodial activity of thiazinoquinone compds. and on their putative mechanism of action.

Exploring the antimalarial potential of the methoxy-​thiazinoquinone scaffold: Identification of a new lead candidate

Imperatore, Concetta
Co-primo
;
Persico, Marco
Co-primo
;
Senese, Maria;Aiello, Anna;Casertano, Marcello;Luciano, Paolo;Fattorusso, Caterina
Penultimo
;
Menna, Marialuisa
Ultimo
2019

Abstract

A small library of antiplasmodial methoxy-​thiazinoquinones, rationally designed on the model of the previously identified hit 1, has been prepd. by a simple and inexpensive procedure. The synthetic derivs. have been subjected to in vitro pharmacol. screening, including antiplasmodial and toxicity assays. These studies afforded a new lead candidate, compd. 9, endowed with higher antiplasmodial potency compared to 1, a good selectivity index when tested against a panel of mammalian cells, no toxicity against RBCs, a synergistic antiplasmodial action in combination with dihydroartemisinin, and a promising inhibitory activity on stage V gametocyte growth. Computational studies provided useful insights into the structural requirements needed for the antiplasmodial activity of thiazinoquinone compds. and on their putative mechanism of action.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/737484
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