Antiplasmodial Activity of p-Substituted Benzyl Thiazinoquinone Derivatives and Their Potential against Parasitic Infections
thiazinoquinones, Plasmodium falciparum, quinone-derived antimalarial agents, marine inspired compounds, cytotoxicity, antiparasitic agents
Malaria is a life-threatening disease and, what is more, the resistance to available antimalarial drugs is a recurring problem. The resistance of Plasmodium falciparum malaria parasites to previous generations of medicines has undermined malaria control efforts and reversed gains in child survival. This paper describes a continuation of our ongoing efforts to investigate the effects against Plasmodium falciparum strains and human microvascular endothelial cells (HMEC-1) of a series of methoxy p-benzyl-substituted thiazinoquinones designed starting from a pointed antimalarial lead candidate. The data obtained from the newly tested compounds expanded the structure–activity relationships (SARs) of the thiazinoquinone scaffold, indicating that antiplasmodial activity is not affected by the inductive effect but rather by the resonance effect of the introduced group at the para position of the benzyl substituent. Indeed, the current survey was based on the evaluation of antiparasitic usefulness as well as the selectivity on mammalian cells of the tested p-benzyl-substituted thiazinoquinones, upgrading the knowledge about the active thiazinoquinone scaffold.
Marcello Casertano, Marialuisa Menna, Caterina Fattorusso, Nicoletta Basilico, Silvia Parapini, Marco Persico, Concetta Imperatore