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.
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.
|Titolo:||Exploring the antimalarial potential of the methoxy-thiazinoquinone scaffold: Identification of a new lead candidate|
BASILICO, NICOLETTA (Corresponding)
|Parole Chiave:||Antimalarial; DFT calculations; Organic synthesis; Reactive radical species; Redox-based mechanism of action; Thiazinoquinones; Biochemistry; Molecular Biology; Drug Discovery3003 Pharmaceutical Science; Organic Chemistry|
|Settore Scientifico Disciplinare:||Settore MED/04 - Patologia Generale|
|Data di pubblicazione:||apr-2019|
|Data ahead of print / Data di stampa:||3-gen-2019|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.bioorg.2018.12.031|
|Appare nelle tipologie:||01 - Articolo su periodico|