New phenalenone analogues with improved activity against Leishmania species
ABSTRACT: 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 p...
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Format: | Article |
Language: | English |
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Elsevier
2020-12-01
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Series: | Biomedicine & Pharmacotherapy |
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Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332220310076 |
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Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Atteneri López-Arencibia Carlos J. Bethencourt-Estrella Mónica B. Freijo María Reyes-Batlle Ines Sifaoui Desirée San Nicolás-Hernández Grant McNaughton-Smith Jacob Lorenzo-Morales Teresa Abad-Grillo José E. Piñero |
spellingShingle |
Atteneri López-Arencibia Carlos J. Bethencourt-Estrella Mónica B. Freijo María Reyes-Batlle Ines Sifaoui Desirée San Nicolás-Hernández Grant McNaughton-Smith Jacob Lorenzo-Morales Teresa Abad-Grillo José E. Piñero New phenalenone analogues with improved activity against Leishmania species Biomedicine & Pharmacotherapy Phenalenones Leishmania amazonensis apoptosis-like chemotherapy |
author_facet |
Atteneri López-Arencibia Carlos J. Bethencourt-Estrella Mónica B. Freijo María Reyes-Batlle Ines Sifaoui Desirée San Nicolás-Hernández Grant McNaughton-Smith Jacob Lorenzo-Morales Teresa Abad-Grillo José E. Piñero |
author_sort |
Atteneri López-Arencibia |
title |
New phenalenone analogues with improved activity against Leishmania species |
title_short |
New phenalenone analogues with improved activity against Leishmania species |
title_full |
New phenalenone analogues with improved activity against Leishmania species |
title_fullStr |
New phenalenone analogues with improved activity against Leishmania species |
title_full_unstemmed |
New phenalenone analogues with improved activity against Leishmania species |
title_sort |
new phenalenone analogues with improved activity against leishmania species |
publisher |
Elsevier |
series |
Biomedicine & Pharmacotherapy |
issn |
0753-3322 |
publishDate |
2020-12-01 |
description |
ABSTRACT: 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. |
topic |
Phenalenones Leishmania amazonensis apoptosis-like chemotherapy |
url |
http://www.sciencedirect.com/science/article/pii/S0753332220310076 |
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1721432873000501248 |
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doaj-6b595ba182bf4d6ab05591208f213aa82021-05-21T04:18:20ZengElsevierBiomedicine & Pharmacotherapy0753-33222020-12-01132110814New phenalenone analogues with improved activity against Leishmania speciesAtteneri López-Arencibia0Carlos J. Bethencourt-Estrella1Mónica B. Freijo2María Reyes-Batlle3Ines Sifaoui4Desirée San Nicolás-Hernández5Grant McNaughton-Smith6Jacob Lorenzo-Morales7Teresa Abad-Grillo8José E. Piñero9Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez, S/N, 38203 La Laguna, Tenerife, Islas Canarias, Spain; Departamento de Obstetricia y Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal y Forense y Parasitología, Universidad de La Laguna, Tenerife, Spain; Red de Investigación Colaborativa en Enfermedades Tropicales (RICET), Instituto de Salud Carlos III, Madrid, SpainInstituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez, S/N, 38203 La Laguna, Tenerife, Islas Canarias, SpainInstituto Universitario de Bio-Orgánica ‘Antonio González’, Departamento de Química Orgánica, Universidad de La Laguna, Avda. Fco. Sánchez 2, 38206 La Laguna, Tenerife, Islas Canarias, SpainInstituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez, S/N, 38203 La Laguna, Tenerife, Islas Canarias, Spain; Red de Investigación Colaborativa en Enfermedades Tropicales (RICET), Instituto de Salud Carlos III, Madrid, SpainInstituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez, S/N, 38203 La Laguna, Tenerife, Islas Canarias, Spain; Red de Investigación Colaborativa en Enfermedades Tropicales (RICET), Instituto de Salud Carlos III, Madrid, SpainInstituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez, S/N, 38203 La Laguna, Tenerife, Islas Canarias, SpainCentro Atlántico del Medicamento S.A (CEAMED S.A.), PCTT, La Laguna, Tenerife, Islas Canarias, SpainInstituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez, S/N, 38203 La Laguna, Tenerife, Islas Canarias, Spain; Departamento de Obstetricia y Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal y Forense y Parasitología, Universidad de La Laguna, Tenerife, Spain; Red de Investigación Colaborativa en Enfermedades Tropicales (RICET), Instituto de Salud Carlos III, Madrid, Spain; Corresponding author at: Instituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez, S/N, 38203 La Laguna, Tenerife, Islas Canarias, Spain.Instituto Universitario de Bio-Orgánica ‘Antonio González’, Departamento de Química Orgánica, Universidad de La Laguna, Avda. Fco. Sánchez 2, 38206 La Laguna, Tenerife, Islas Canarias, SpainInstituto Universitario de Enfermedades Tropicales y Salud Pública de Canarias, Universidad de La Laguna, Avda. Astrofísico Fco. Sánchez, S/N, 38203 La Laguna, Tenerife, Islas Canarias, Spain; Departamento de Obstetricia y Ginecología, Pediatría, Medicina Preventiva y Salud Pública, Toxicología, Medicina Legal y Forense y Parasitología, Universidad de La Laguna, Tenerife, Spain; Red de Investigación Colaborativa en Enfermedades Tropicales (RICET), Instituto de Salud Carlos III, Madrid, SpainABSTRACT: 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.http://www.sciencedirect.com/science/article/pii/S0753332220310076PhenalenonesLeishmania amazonensisapoptosis-likechemotherapy |