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; Persico, Marco; Senese, Maria; Aiello, Anna; Casertano, Marcello; Luciano, Paolo; Basilico, Nicoletta; Parapini, Silvia; Paladino, Antonella; Fattorusso, Caterina; Menna, Marialuisa. - In: BIOORGANIC CHEMISTRY. - ISSN 0045-2068. - 85:(2019), pp. 240-252. [10.1016/j.bioorg.2018.12.031]
Exploring the antimalarial potential of the methoxy-thiazinoquinone scaffold: Identification of a new lead candidate
Imperatore, ConcettaCo-primo
;Persico, MarcoCo-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.File | Dimensione | Formato | |
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