Metabolite profile of Nectandra oppositifolia Nees & Mart. and assessment of antitrypanosomal activity of bioactive compounds through efficiency analyses

Author(s)

Alves Conserva, Geanne A. ^[1] ; Quiros-Guerrero, Luis M. ^{[2, 3]} ; Costa-Silva, Thais A. ^[1] ; Marcourt, Laurence ^{[2, 3]} ; Pinto, Erika G. ^[4] ; Tempone, Andre G. ^[5] ; Fernandes, Joao Paulo S. ^[6] ; Wolfender, Jean-Luc ^{[2, 3]} ; Queiroz, Emerson F. ^{[2, 3]} ; Lago, Joao Henrique G. ^[1]

Affiliation

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

^[2] Univ Geneva, Sch Pharmaceut Sci, Geneva - Switzerland

^[3] Univ Geneva, Inst Pharmaceut Sci Western Switzerland, Geneva - Switzerland

^[4] Univ Dundee, Sch Life Sci, Drug Discovery Unit, Dundee - Scotland

^[5] Adolfo Lutz Inst, Ctr Parasitol & Mycol, Sao Paulo - Brazil

^[6] Univ Fed Sao Paulo, Dept Pharmaceut Sci, Diadema, SP - Brazil

• Document type: Journal article
• Source: PLoS One; v. 16, n. 2 FEB 25 2021.
• Web of Science Citations: 1

Abstract

EtOH extracts from the leaves and twigs of Nectandra oppositifolia Nees \& Mart. shown activity against amastigote forms of Trypanosoma cruzi. These extracts were subjected to successive liquid-liquid partitioning to afford bioactive CH2Cl2 fractions. UHPLC-TOF-HRMS/MS and molecular networking were used to obtain an overview of the phytochemical composition of these active fractions. Aiming to isolate the active compounds, both CH2Cl2 fractions were subjected to fractionation using medium pressure chromatography combined with semi-preparative HPLC-UV. Using this approach, twelve compounds (1-12) were isolated and identified by NMR and HRMS analysis. Several isolated compounds displayed activity against the amastigote forms of T. cruzi, especially ethyl protocatechuate (7) with EC50 value of 18.1 mu M, similar to positive control benznidazole (18.7 mu M). Considering the potential of compound 7, protocatechuic acid and its respective methyl (7a), n-propyl (7b), n-butyl (7c), n-pentyl (7d), and n-hexyl (7e) esters were tested. Regarding antitrypanosomal activity, protocatechuic acid and compound 7a were inactive, while 7b-7e exhibited EC50 values from 20.4 to 11.7 mu M, without cytotoxicity to mammalian cells. These results suggest that lipophilicity and molecular complexity play an important role in the activity while efficiency analysis indicates that the natural compound 7 is a promising prototype for further modifications to obtain compounds effective against the intracellular forms of T. cruzi. (AU)

• FAPESP's process: 18/18975-1 - Dereplication profile of Nectandra oppositifolia Nees & Mart. (Lauraceae): identification and molecular characterization of antiparasitic metabolites
• Grantee: Geanne Alexsandra Alves Conserva
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• 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
• FAPESP's process: 16/20633-6 - Bioactive metabolites from Nectandra oppositifolia Nees & Mart. (Lauraceae): molecular characterization, in vitro and in vivo antiparasitic potential evaluation and determination of mechanism of action
• Grantee: Geanne Alexsandra Alves Conserva
• Support Opportunities: Scholarships in Brazil - Doctorate
• 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: 15/23403-9 - Rational Pre-Clinical Study of New Drug Candidates Against Neglected Protozoan Diseases Using Pharmacokinetic Approaches
• Grantee: André Gustavo Tempone Cardoso
• Support Opportunities: Regular Research Grants