Melatonin action in Plasmodium infection: Searching for molecules that modulate the asexual cycle as a strategy to impair the parasite cycle

Autor(es)

Pereira, Pedro H. S. ^[1] ; Garcia, Celia R. S. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo, SP - Brazil

• Tipo de documento: Artigo de Revisão
• Fonte: Journal of Pineal Research; v. 70, n. 1 OCT 2020.
• Citações Web of Science: 0

Resumo

Half of the world's population lives in countries at risk of malaria infection, which results in approximately 450,000 deaths annually. Malaria parasites infect erythrocytes in a coordinated manner, with cycle durations in multiples of 24 hours, which reflects a behavior consistent with the host's circadian cycle. Interference in cycle coordination can help the immune system to naturally fight infection. Consequently, there is a search for new drugs that interfere with the cycle duration for combined treatment with conventional antimalarials. Melatonin appears to be a key host hormone responsible for regulating circadian behavior in the parasite cycle. In addition to host factors, there are still unknown factors intrinsic to the parasite that control the cycle duration. In this review, we present a series of reports of indole compounds and melatonin derivatives with antimalarial activity that were tested on several species of Plasmodium to evaluate the cytotoxicity to parasites and human cells, in addition to the ability to interfere with the development of the erythrocytic cycle. Most of the reported compounds had an IC50 value in the low micromolar range, without any toxicity to human cells. Triptosil, an indole derivative of melatonin, was able to inhibit the effect of melatonin in vitro without causing changes to the parasitemia. The wide variety of tested compounds indicates that it is possible to develop a compound capable of safely eliminating parasites from the host and interfering with the life cycle, which is promising for the development of new combined therapies against malaria. (AU)

• Processo FAPESP: 18/07177-7 - EMU concedido no processo 2011/51295-5: image system
• Beneficiário: Célia Regina da Silva Garcia
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 17/08684-7 - Decodificar aspectos da biologia celular e molecular do Plasmodium como uma ferramenta para desenvolver novos antimaláricos
• Beneficiário: Célia Regina da Silva Garcia
• Modalidade de apoio: Auxílio à Pesquisa - Temático