Exploring the antimalarial potential of the methoxy-thiazinoquinone scaffold: Identification of a new lead candidate
Articolo
Data di Pubblicazione:
2019
Citazione:
Exploring the antimalarial potential of the methoxy-thiazinoquinone scaffold: Identification of a new lead candidate / C. Imperatore, M. Persico, M. Senese, A. Aiello, M. Casertano, P. Luciano, N. Basilico, S. Parapini, A. Paladino, C. Fattorusso, M. Menna. - In: BIOORGANIC CHEMISTRY. - ISSN 0045-2068. - 85(2019 Apr), pp. 240-252. [10.1016/j.bioorg.2018.12.031]
Abstract:
A small library of antiplasmodial methoxy-thiazinoquinones, rationally designed on the model of the previously identified hit 1, has been prepared by a simple and inexpensive procedure. The synthetic derivatives have been subjected to in vitro pharmacological screening, including antiplasmodial and toxicity assays. These studies afforded a new lead candidate, compound 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 compounds and on their putative mechanism of action.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
Antimalarial; DFT calculations; Organic synthesis; Reactive radical species; Redox-based mechanism of action; Thiazinoquinones; Biochemistry; Molecular Biology; Drug Discovery3003 Pharmaceutical Science; Organic Chemistry
Elenco autori:
C. Imperatore, M. Persico, M. Senese, A. Aiello, M. Casertano, P. Luciano, N. Basilico, S. Parapini, A. Paladino, C. Fattorusso, M. Menna
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