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

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: CHEMISTRY & BIODIVERSITY; v. 18, n. 4 MAR 2021.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 18/10279-6 - Selection and Optimization of New Drug Candidates for Leishmaniasis and Chagas Disease
• Grantee: André Gustavo Tempone Cardoso
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/07885-1 - Biomolecules from plant species of remnant areas of the Atlantic Forest and Cerrado to treat neglected tropical diseases - chemical and pharmacological aspects
• Grantee: João Henrique Ghilardi Lago
• Support Opportunities: BIOTA-FAPESP Program - Regular Research Grants