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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
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]
Total Authors: 6
Affiliation:
[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
Total Affiliations: 4
Document type: Journal article
Source: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY; v. 78, p. 375-382, MAY 6 2014.
Web of Science Citations: 31
Abstract

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)

FAPESP's process: 11/51295-5 - Functional genomics in Plasmodium
Grantee:Célia Regina da Silva Garcia
Support type: Research Projects - Thematic Grants