New phenalenone analogues with improved activity against Leishmania species
| Autor: | Mónica Blanco Freijo, Desirée San Nicolás-Hernández, Teresa Abad-Grillo, Jacob Lorenzo-Morales, Carlos J. Bethencourt-Estrella, Ines Sifaoui, Grant McNaughton-Smith, María Reyes-Batlle, Atteneri López-Arencibia, José E. Piñero |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Drug Programmed cell death Phosphorylcholine media_common.quotation_subject Phenalenones Antiprotozoal Agents Apoptosis RM1-950 chemotherapy 03 medical and health sciences 0302 clinical medicine medicine Parasite hosting media_common Leishmania Membrane Potential Mitochondrial Pharmacology Membrane potential Miltefosine biology Chemistry Depolarization General Medicine Phenalenes biology.organism_classification apoptosis-like In vitro 030104 developmental biology Biochemistry 030220 oncology & carcinogenesis Therapeutics. Pharmacology medicine.drug Leishmania amazonensis |
| Zdroj: | Biomedicine & Pharmacotherapy, Vol 132, Iss, Pp 110814-(2020) |
| ISSN: | 0753-3322 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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