Antitrypanosomal activity and effect in plasma membrane permeability of (-)-bornyl p-coumarate isolated from Piper cernuum (Piperaceae)

Author(s)

Morais, Thiago R. ^[1] ; Costa-Silva, Thais A. ^[2] ; Ferreira, Daiane D. ^[3] ; Novais, Bianca J. ^[1] ; Torrecilhas, Ana Claudia T. ^[1] ; Tempone, Andre G. ^[3] ; Lago, Joao Henrique G. ^[2]

Affiliation

^[1] Univ Fed Sao Paulo, Inst Environm Chem & Pharmaceut Sci, BR-09972270 Sao Paulo - Brazil

^[2] Univ Fed ABC, Ctr Nat Sci & Humanities, BR-09210580 Santo Andre, SP - Brazil

^[3] Adolfo Lutz Inst, Ctr Parasitol & Mycol, BR-01246000 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: BIOORGANIC CHEMISTRY; v. 89, AUG 2019.
• Web of Science Citations: 1

Abstract

This work describes the isolation of six metabolites from leaves and branches of Piper cernuum (Piperaceae): ( - )-cubebin (1), ( - )-hinokinin (2), ( - )-kusunokinin (3), trans-dehydroagarofuran (4), 11-hydroxi-4,5-secoeudesmane-4,5-dione (5), and ( - )-bornyl p-coumarate (6). Antitrypanosomal activity and toxicity of purified compounds were performed in vitro against trypomastigote forms of Trypanosoma cruzi and NCTC cells, respectively. Compounds 2, 3 and 5 showed moderate activities with IC50, values of 33.1, 31.8 and 45.9 mu M, respectively, while compounds 1 and 4 were inactive (IC50 > 100 mu M). On the other hand, compound 6 displayed an IC50 value of 2.1 mu M, a selectivity index (SI) of 18 and induced a considerable interference in the plasma membrane permeability (87%) in trypomastigotes of T. cruzi. Additionally, the lethal effect of compound 6 in T. cruzi could be associated to the plasma membrane permeability. Finally, experiments using scanning electron microscopy (SEM) confirmed the obtained results in which was possible to observe total alteration parasites topography after treatment with compound 6 in comparison to untreated parasites. These data indicated that the lethal action of compound 6 is directly related to structural disruption of the membrane. (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