Synthetic indole and melatonin derivatives exhibit antimalarial activity on the cell cycle of the human malaria parasite Plasmodium falciparum

Autor(es)

Schuck, Desiree C. ^{[1, 2]} ; Jordao, Alessandro K. ^{[3, 4]} ; Nakabashi, Myna ^[1] ; Cunha, Anna C. ^[3] ; Ferreira, Vitor F. ^[3] ; Garcia, Celia R. S. ^{[1, 2]}

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Inst Biociencias, Dept Fisiol, BR-05508900 Sao Paulo - Brazil

^[2] Univ Sao Paulo, Inst Ciencias Biomed, Dept Parasitol, BR-05508900 Sao Paulo - Brazil

^[3] Univ Fed Fluminense, Dept Quim Organ, Programa Posgrad Quim, BR-24020141 Niteroi, RJ - Brazil

^[4] Ctr Univ Estadual Zona Oeste, BR-23070200 Rio De Janeiro, RJ - Brazil

• Tipo de documento: Artigo Científico
• Fonte: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY; v. 78, p. 375-382, MAY 6 2014.
• Citações Web of Science: 28

Resumo

Discovering the mechanisms by which cell signaling controls the cell cycle of the human malaria parasite Plasmodium falciparum is fundamental to designing more effective antimalarials. To better understand the impacts of melatonin structure and function on the cell cycle of P. falciparum, we have synthesized two families of structurally-related melatonin compounds (7-11 and 12-16). All synthesized melatonin analogs were assayed in P. falciparum culture and their antimalarial activities were measured by flow cytometry. We have found that the chemical modification of the carboxamide group attached at C-3 position of the indole ring of melatonin (6) was crucial for the action of the indole-related compounds on the P. falciparum cell cycle. Among the melatonin derivatives, only the compounds 12, 13 and 14 were capable of inhibiting the P. falciparum growth in low micromolar IC50. These results open good perspectives for the development of new drugs with novel mechanisms of action. (C) 2014 Elsevier Masson SAS. All rights reserved. (AU)

• Processo FAPESP: 09/53640-1 - P. falciparum: marcadores moleculares de resistência
• Beneficiário: Célia Regina da Silva Garcia
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 11/51295-5 - Genômica funcional em Plasmodium
• Beneficiário: Célia Regina da Silva Garcia
• Modalidade de apoio: Auxílio à Pesquisa - Temático