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The in vitro activity against Leishmania spp. of five novel designed compounds, phenalenone derivatives, is described in this study. Previous works have shown that some phenalenones present leishmanicidal activity, some of which could induce programmed cell death events in L. amazonensis parasites. In this research, we focused on the determination of the programmed cell death evidence by detecting the characteristic features of the apoptosis-like process, such as phosphatidylserine exposure and mitochondrial membrane potential, among others. The results showed that the new derivatives have comparable or better activity and selectivity than the commonly prescribed anti-leishmanial drug. This result was obtained by inducing stronger mitochondrial depolarization or more intense phosphatidylserine exposure than miltefosine, highlighting compound 8 with moreover 9-times better selectivity index. In addition, the new five molecules activated the apoptosis-like process in the parasite. All the signals observed were indicative of the death process that the parasites were undergoing., (Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.)

A collection of N-substituted quinolin-2(1H)-ones were screened against a panel of clinically relevant protozoa (Leishmania, Trypanosoma and Acanthamoeba). Three quinolin-2(1H)-one compounds were identified as selective anti-Acanthamoeba agents. Further assessment revealed that these compounds were active against both trophozoite and cyst forms of A. castellanii Neff, and caused protozoa death via apoptosis. The data presented herein identify N-acyl quinolin-2(1H)-ones as a promising new class of selective anti-Acanthamoeba agents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The in vitro activity against Leishmania spp. of a novel group of compounds, phenalenone derivatives, is described in this study. Previous studies have shown that some phenalenones present leishmanicidal activity, and induce a decrease in the mitochondrial membrane potential in L. amazonensis parasites, so in order to elucidate the evidence of programmed cell death occurring inside the promastigote stage, different assays were performed in two different species of Leishmania., Methods: We focused on the determination of the programmed cell death evidence by detecting the characteristic features of the apoptosis-like process, such as phosphatidylserine exposure, mitochondrial membrane potential, and chromatin condensation among others., Results: The results showed that four molecules activated the apoptosis-like process in the parasite. All the signals observed were indicative of the death process that the parasites were undergoing., Conclusions: The present results highlight the potential use of phenalenone derivatives against Leishmania species and further studies should be undertaken to establish them as novel leishmanicidal therapeutic agents.

Screening of a designed collection of mono-substituted amino-1H-phenalen-1-ones against promastigote forms of L. donovani and L. amazonensis, identified seven compounds with anti-leishmanial activities comparable or better than the commonly prescribed anti-leishmanial drug, miltefosine. Structure-activity analysis revealed that appendages containing a basic tertiary nitrogen were favored, and that the position of the appendage also affected their potency. Like miltefosine, several of these active compounds significantly reduced the mitochondrial membrane potential in promastigotes. Further studies in amastigotes of L. amazonensis revealed that compounds 14, 15 and 33 were more active and more selective than miltefosine, with sub-micromolar potencies and selectivity indices >100., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

A set of derivatives encompassing structural modifications on the privileged phenalenone scaffold were assessed for their antiparasitic activities against the most clinically relevant forms of trypanosomiasis and leishmaniasis. Several compounds exhibited leishmanicidal effects at levels comparable or better than the reference drug pentamidine, while the parent phenalenone was shown to have a level of activity against Trypanosoma cruzi comparable to the marketed drug benznidazole., (Copyright 2010 Elsevier Ltd. All rights reserved.)