Aporphine Alkaloids from Ocotea puberula with Anti-Trypanosoma Cruzi Potential - Activity of Dicentrine-beta-N-Oxide in the Plasma Membrane Electric Potentials

Autor(es)

Barbosa, Henrique ^[1] ; Costa-Silva, Thais A. ^[1] ; Alves Conserva, Geanne A. ^[1] ; Araujo, Adelson J. ^[2] ; Lordello, Ana Luisa L. ^[2] ; Antar, Guilherme M. ^[3] ; Amaral, Maiara ^[4] ; Soares, Marisi G. ^[5] ; Tempone, Andre G. ^[4] ; Lago, Joao Henrique G. ^[1]

Afiliação do(s) autor(es)

^[1] Fed Univ ABC, Ctr Nat & Human Sci, BR-09210580 Santo Andre, SP - Brazil

^[2] Univ Fed Parana, Dept Chem, BR-81531980 Curitiba, PR - Brazil

^[3] Univ Sao Paulo, Inst Biosci, BR-05508090 Sao Paulo, SP - Brazil

^[4] Adolfo Lutz Inst, Ctr Parasitol & Mycol, BR-01246902 Sao Paulo, SP - Brazil

^[5] Univ Fed Alfenas, Inst Chem, BR-37130001 Alfenas, MG - Brazil

• Tipo de documento: Artigo Científico
• Fonte: CHEMISTRY & BIODIVERSITY; v. 18, n. 4 MAR 2021.
• Citações Web of Science: 0

Resumo

One new aporphine, dicentrine-beta-N-oxide (1), together with five related known alkaloids dehydrodicentrine (2), predicentrine (3), N-methyllaurotetanine (4), cassythicine (5), and dicentrine (6) were isolated from the leaves of Ocotea puberula (Lauraceae). Antiprotozoal activity of the isolated compounds was evaluated in vitro against trypomastigote forms of Trypanosoma cruzi. Among the tested compounds, alkaloid 1 exhibited higher potential with EC50 value of 18.2 mu M and reduced toxicity against NCTC cells (CC50>200 mu M - SI>11.0), similar to positive control benznidazole (EC50 of 17.7 mu M and SI=10.7). Considering the promising results of dicentrine-beta-N-oxide (1) against trypomastigotes, the mechanism of parasite death caused by this alkaloid was investigated. As observed, this compound reached the plasma membrane electric potential directly after 2 h of incubation and triggered mitochondrial depolarization, which probably leads to trypomastigote death. Therefore, dicentrine-beta-N-oxide (1), reported for the first time in this work, can contribute to future works for the development of new trypanocidal agents. (AU)

• Processo FAPESP: 18/10279-6 - Seleção e Otimização de Novos Candidatos a Fármacos para Leishmaniose e Doença de Chagas
• Beneficiário: André Gustavo Tempone Cardoso
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/07885-1 - Biomoléculas oriundas de espécies vegetais de áreas remanescentes da Mata Atlântica e do Cerrado para tratamento de doenças tropicais negligenciadas - aspectos químicos e farmacológicos
• Beneficiário: João Henrique Ghilardi Lago
• Modalidade de apoio: Auxílio à Pesquisa - Programa BIOTA - Regular