Anti-leishmanial and anti-trypanosomal activities of 1,4-dihydropyridines: In vitro evaluation and structure-activity relationship study

Author(s)

Reimao, Juliana Q. ^[1] ; Scotti, Marcus T. ^[2] ; Tempone, Andre G. ^[1]

Affiliation

^[1] Inst Adolfo Lutz Registro, Dept Parasitol, Lab Appl Toxinol Antiparasit Drugs, BR-01246902 Sao Paulo - Brazil

^[2] Univ Fed Paraiba, Ctr Appl Sci & Educ, Rio Tinto, PB - Brazil

• Document type: Journal article
• Source: Bioorganic & Medicinal Chemistry; v. 18, n. 22, p. 8044-8053, NOV 15 2010.
• Web of Science Citations: 41

Abstract

Leishmaniasis and Chagas' disease constitute a relevant health and socio-economic problem in Latin America, Africa, and Asia. The therapeutic interventions rely on inefficient and highly toxic drugs with systemic side effects in patients. Considering the multiple biological activities of the calcium channel blockers and the high versatility of 1,4-dihydropyridines, eight clinically used 1,4-dihydropyridines (azelnidipine, amlodipine, cilnidipine, lercanidipine, nicardipine, nifedipine, nimodipine and nitrendipine) were in vitro tested against Leishmania and Trypanosoma cruzi parasites, and their cytotoxicity was tested against mammalian cells. In addition, a QSAR study was performed in order to delineate further structural requirements for the anti-protozoan activity and to predict the biological potency of 1,4-dihydropyridines. The tested compounds were effective against Leishmania (L.) amazonensis, Leishmania (V.) braziliensis, Leishmania (L.) chagasi, and Leishmania (L.) major promastigotes, L. (L.) chagasi intracellular amastigotes and T. cruzi trypomastigotes with 50% inhibitory concentration (IC(50)) values in the range of 2.6-181 mu M. The QSAR provided useful information about the structural features of the anti-protozoan activities, including diphenylpropyl and diphenylmethylazetidin groups at position 4 of the 1,4-dihydropyridine ring, allowing the prediction of two novel potential anti-protozoan analogs. (C) 2010 Elsevier Ltd. All rights reserved. (AU)

• FAPESP's process: 08/11434-3 - Therapeutic combinations in Visceral Leishmaniasis: the antileishmanial potential of calcium channel blockers
• Grantee: Juliana Quero Reimão Dalla Zanna
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 08/09260-7 - Therapeutic combinations for visceral leishmaniasis: the antileishmanial potential of calcium channel blockers and the use of liposomal nanoformulations
• Grantee: André Gustavo Tempone Cardoso
• Support Opportunities: Regular Research Grants