A number of quinones have been shown to be effective antimalarials; the antiplasmodial activity of quinone structures is most likely related to the most prominent chemical feature of these kind of molecules, that is their ability to undergo redox cycling. Several natural quinones exhibited antiplasmodial activity; pharmacological studies on these compounds evidenced that the presence of a dioxothiazine moiety fused to the quinone moiety to give the thiazinoquinone scaffold enhances the activity. On this basis, we have started a study aimed to prepare thiazinoquinone derivatives with antiplasmodial activity using marine natural products as lead compounds. In this communication the synthesis of a series of analogues of the marine derived thiazinoquinones Aplidinones A and B (figure 2), isolated from the Mediterranean ascidian Aplidium conicum (figure 1), is reported. Most of synthetic derivatives, with different substituents and simplified alkyl chains, have shown a significant pharmacological activity and the redox properties of compounds 1-12 have been investigated by computational studies and electrochemical assays. The synthetic derivatives (figure 2) prepared in the course of this study have been tested in vitro against two strains (CQ-S, D10 and CQ-R, W2) of Plasmodium falciparum; the toxicity of the active compounds has been evaluated against human microvascular endothelial cells (HMEC-1).

Antimalarial Potential Of Synthetic Thiazinoquinones

Maria Senese;Anna Aiello;Paolo Luciano;Caterina Fattorusso;Concetta Imperatore;Marco Persico;Marialuisa Menna
2015

Abstract

A number of quinones have been shown to be effective antimalarials; the antiplasmodial activity of quinone structures is most likely related to the most prominent chemical feature of these kind of molecules, that is their ability to undergo redox cycling. Several natural quinones exhibited antiplasmodial activity; pharmacological studies on these compounds evidenced that the presence of a dioxothiazine moiety fused to the quinone moiety to give the thiazinoquinone scaffold enhances the activity. On this basis, we have started a study aimed to prepare thiazinoquinone derivatives with antiplasmodial activity using marine natural products as lead compounds. In this communication the synthesis of a series of analogues of the marine derived thiazinoquinones Aplidinones A and B (figure 2), isolated from the Mediterranean ascidian Aplidium conicum (figure 1), is reported. Most of synthetic derivatives, with different substituents and simplified alkyl chains, have shown a significant pharmacological activity and the redox properties of compounds 1-12 have been investigated by computational studies and electrochemical assays. The synthetic derivatives (figure 2) prepared in the course of this study have been tested in vitro against two strains (CQ-S, D10 and CQ-R, W2) of Plasmodium falciparum; the toxicity of the active compounds has been evaluated against human microvascular endothelial cells (HMEC-1).
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/738352
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