Structural and biological characterization of synthetic Guanidines as potential agents against cutaneous and visceral Leishmaniasis

• Grant number: 21/02595-8
• Support Opportunities: Regular Research Grants
• Start date: March 01, 2022
• End date: May 31, 2024
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Eduardo Rene Perez Gonzalez
• Grantee: Eduardo Rene Perez Gonzalez
• Host Institution: Faculdade de Ciências e Tecnologia (FCT). Universidade Estadual Paulista (UNESP). Campus de Presidente Prudente. Presidente Prudente , SP, Brazil

Abstract

Leishmaniasis are infectious-parasitic diseases caused by parasitic protozoa of the Trypanosomatidae family. This project aims to search for new compounds for the treatment of this important neglected disease whose treatments present several problems, such as high toxicity and occurrence of resistant strains. Several guanidine derivatives have been studied for the treatment of neglected diseases and some of them have been tested against Leishmania spp. The main goal of this work is to synthesize, to characterize, and to evaluate the antileishmanial properties of newly synthesized compounds containing the guanidine nuclei. The novel guanidine compounds will be analyzed by mass spectrometry with electronic and electro-spray ionization as well as by nuclear magnetic resonance of 1H, 13C, 15N and other nuclei. Herein, the activity of guanidines against the promastigote and amastigote forms of Leishmania infantum, Leishmania braziliense and Leishmania amazonensis, will be evaluated. Enzyme inhibition assays will be performed for the enzyme cisteine protease. Pre-clinical assays (in vivo studies) will be also performed in order to evaluate the antileishmanial efficacy of those compounds that present the highest activity (IC50<10uM) and the lowest toxicity. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

COSTA, NATALIA C. S.; DOS ANJOS, LUANA RIBEIRO; DE SOUZA, JOAO VICTOR MARCELINO; BRASIL, MARIA CAROLINA OLIVEIRA DE ARRUDA; MOREIRA, VITOR PARTITE; GRAMINHA, MARCIA A. S.; LUBEC, GERT; GONZALEZ, EDUARDO RENE P.; CILLI, EDUARDO MAFFUD. Development of New Leishmanicidal Compounds via Bioconjugation of Antimicrobial Peptides and Antileishmanial Guanidines. ACS OMEGA, v. 8, n. 37, p. 9-pg., 2023-09-06. (21/02595-8, 22/05411-8)

MOREIRA, VITOR PARTITE; DA SILVA MELA, MICHELE FERREIRA; DOS ANJOS, LUANA RIBEIRO; SARAIVA, LEONARDO FIGUEIREDO; VELASQUEZ, ANGELA M. ARENAS; KALABA, PREDRAG; FABISIKOVA, ANNA; CLEMENTINO, LEANDRO DA COSTA; AUFY, MOHAMMED; STUDENIK, CHRISTIAN; et al. Novel Selective and Low-Toxic Inhibitor of LmCPB2.8 Delta CTE (CPB) One Important Cysteine Protease for Leishmania Virulence. BIOMOLECULES, v. 12, n. 12, p. 21-pg., 2022-12-01. (18/00581-7, 20/04415-4, 16/19289-9, 17/03552-5, 18/23015-7, 21/02595-8)