دورية أكاديمية
أعرض في EDS

Bioenergetics impairment of Trypanosoma cruzi by the antihypertensive manidipine: A drug repurposing strategy.

التفاصيل البيبلوغرافية
العنوان: Bioenergetics impairment of Trypanosoma cruzi by the antihypertensive manidipine: A drug repurposing strategy.
المؤلفون: Correa ITS; Centre for Parasitology and Mycology, Instituto Adolfo Lutz, São Paulo, SP, 01246-000, Brazil., da Costa-Silva TA; Center of Natural Sciences and Humanities, Federal University of ABC, Santo Andre, SP, 09210-180, Brazil. Electronic address: tha_isbio@yahoo.com.br., Tempone AG; Centre for Parasitology and Mycology, Instituto Adolfo Lutz, São Paulo, SP, 01246-000, Brazil. Electronic address: andre.tempone@ial.sp.gov.br.
المصدر: Acta tropica [Acta Trop] 2021 Feb; Vol. 214, pp. 105768. Date of Electronic Publication: 2020 Nov 25.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Elsevier Country of Publication: Netherlands NLM ID: 0370374 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-6254 (Electronic) Linking ISSN: 0001706X NLM ISO Abbreviation: Acta Trop Subsets: MEDLINE
أسماء مطبوعة: Publication: Amsterdam : Elsevier
Original Publication: Basel.
مواضيع طبية MeSH: Drug Repositioning*, Antihypertensive Agents/*pharmacology , Dihydropyridines/*pharmacology , Nitrobenzenes/*pharmacology , Piperazines/*pharmacology , Trypanosoma cruzi/*drug effects, Animals ; Cell Line ; Macaca mulatta ; Membrane Potential, Mitochondrial/drug effects ; Mice ; Mice, Inbred BALB C ; Trypanocidal Agents/pharmacology ; Trypanosoma cruzi/metabolism
مستخلص: Considering the lack of effective and safe therapy for the treatment of Chagas disease, the antihypertensive drug manidipine (MDP) was in vitro evaluated against Trypanosoma cruzi. The bioenergetics of trypomastigotes was studied in the presence of the drug using fluorimetric and luminescent assays. Manidipine showed a potent antiparasitic activity, with IC 50 values of 0.1 μM (intracellular amastigotes) and 3 μM (trypomastigotes), resulting in a promising selectivity index against the amastigotes (>1459). Using fluorimetric analysis, the drug showed depolarisation of the electric potential of the plasma membrane with no alteration of the permeability. A decrease in ATP levels suggested a bioenergetic alteration of the mitochondria, which was confirmed by the depolarisation of the mitochondrial membrane potential and a slight increase of the ROS levels. This is the first study to show the promising in vitro effectiveness of the antihypertensive MDP against T. cruzi, which may represent a candidate for future investigations in animal models.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
فهرسة مساهمة: Keywords: Calcium channel blocker; Drug repositioning; Manidipine; Trypanosoma cruzi
المشرفين على المادة: 0 (Antihypertensive Agents)
0 (Dihydropyridines)
0 (Nitrobenzenes)
0 (Piperazines)
0 (Trypanocidal Agents)
6O4754US88 (manidipine)
تواريخ الأحداث: Date Created: 20201127 Date Completed: 20210512 Latest Revision: 20210512
رمز التحديث: 20221213
DOI: 10.1016/j.actatropica.2020.105768
PMID: 33245907
قاعدة البيانات: MEDLINE
الوصف
تدمد:1873-6254
DOI:10.1016/j.actatropica.2020.105768