Quinolin-(1H)-imines as a new chemotype against leishmaniasis: biological evaluation and mechanistic studies [Mechanisms of Action]

xloma.fota13 shared this article with you from Inoreader Quinolin-(1H)-imines as a new chemotype against leishmaniasis: biological evaluation and mechanistic studies [Mechanisms of Action] Via AAC Accepts: Articles Published Ahead of Print Leishmaniasis is one of the most challenging neglected tropical diseases and remains a global threat to public health. Currently available therapies for leishmaniases present significant drawbacks and are rendered increasingly inefficient due to parasite resistance, urging the need for more effective, safer, and cheaper drugs. In our efforts to identify novel chemical scaffolds for the development of antileishmanial agents, we have screened in house antiplasmodial libraries against axenic and intracellular fo rms of Leishmania infantum, L. amazonensis and L. major. Several of the screened compounds showed IC50 values against intracellular L. infantum parasites in the submicromolar range (1h: IC50 0.9 μM and 1n: IC50 0.7 μM) and selectivity indexes of 11 and 9.7, respectively. Compounds also displayed activity against L. amazonensis and L. major, albeit in the low micromolar range. Mechanistic studies revealed that 1n efficiently inhibits oxygen consumption and significantly decreases the mitochondrial membrane potential in L. infantum axenic amastigotes, suggesting that this chemotype acts, at least in part, by interfering with mitochondrial function. Structure-activity analysis suggests that 1n is a promising antileishmanial lead and emphasize the potential of the quinoline-(1H)-imine chemotype for the future development of new antileishmanial agents. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.