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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Discovery of New Hits as Antitrypanosomal Agents by In Silico and In Vitro Assays Using Neolignan-Inspired Natural Products from Nectandra leucantha

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Author(s):
Araujo, Sheila C. [1] ; Sousa, Fernanda S. [2, 3] ; Costa-Silva, Thais A. [1] ; Tempone, Andre G. [4] ; Lago, Joao Henrique G. [1] ; Honorio, Kathia M. [1, 5]
Total Authors: 6
Affiliation:
[1] Univ Fed ABC, Ctr Ciencias Nat & Humanas, Ave Estados, 5001 Bangu, BR-09210580 Santo Andre, SP - Brazil
[2] Univ Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Rua Prof Arthur Riedel 275, BR-09972271 Diadema, SP - Brazil
[3] Univ Fed Minas Gerais, Dept Fisiol & Biofis, Ave Presidente Antonio Carlos 6627, BR-31270901 Belo Horizonte, MG - Brazil
[4] Adolfo Lutz Inst, Ctr Parasitol & Mycol, Ave Doutor Arnaldo 351, BR-01246000 Sao Paulo, SP - Brazil
[5] Univ Sao Paulo, Escola Artes Ciencias & Humanidades, Rua Arlindo Bettio, 1000 Ermelino Matarazzo, BR-03828000 Sao Paulo, SP - Brazil
Total Affiliations: 5
Document type: Journal article
Source: Molecules; v. 26, n. 14 JUL 2021.
Web of Science Citations: 0
Abstract

In the present study, the phytochemical study of the n-hexane extract from flowers of Nectandra leucantha (Lauraceae) afforded six known neolignans (1-6) as well as one new metabolite (7), which were characterized by analysis of NMR, IR, UV, and ESI-HRMS data. The new compound 7 exhibited potent activity against the clinically relevant intracellular forms of T. cruzi (amastigotes), with an IC50 value of 4.3 mu M and no observed mammalian cytotoxicity in fibroblasts (CC50 > 200 mu M). Based on the results obtained and our previous antitrypanosomal data of 50 natural and semi-synthetic related neolignans, 2D and 3D molecular modeling techniques were employed to help the design of new neolignan-based compounds with higher activity. The results obtained from the models were important to understand the main structural features related to the biological response of the neolignans and to aid in the design of new neolignan-based compounds with better biological activity. Therefore, the results acquired from phytochemical, biological, and in silico studies showed that the integration of experimental and computational techniques consists of a powerful tool for the discovery of new prototypes for development of new drugs to treat CD. (AU)

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 type: BIOTA-FAPESP Program - Regular Research Grants
FAPESP's process: 21/04464-8 - Microbial and plant prototypes as drug candidates for protozoan neglected diseases and multidrug-resistant bacteria
Grantee:André Gustavo Tempone Cardoso
Support type: Regular Research Grants
FAPESP's process: 16/24524-7 - STRUCTURAL ANALYSIS AND MOLECULAR MODELING STUDIES FOR NATURAL AND SYNTHETIC LIGANTS RELATED TO NEGLECTED DISEASES
Grantee:Kathia Maria Honorio
Support type: Regular Research Grants
FAPESP's process: 21/02789-7 - Search for bioactive metabolites with antiparasitic action in plant species from Atlantic Forest and Cerrado regions - a chemical, phenotypical, and metabolomic approach
Grantee:João Henrique Ghilardi Lago
Support type: BIOTA-FAPESP Program - Regular Research Grants