Quinoxaline derivatives as antiparasitic drugs: proof of concept

• Grant number: 13/50680-8
• Support Opportunities: Research Grants - Research Partnership for Technological Innovation - PITE
• Start date: November 01, 2014
• End date: February 28, 2017
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Agreement: GlaxoSmithKline
• Principal Investigator: Arlene Gonçalves Corrêa
• Grantee: Arlene Gonçalves Corrêa
• Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil
• Company: Glaxosmithkline Brasil Ltda
• City: São Carlos
• Associated scholarship(s): 16/13894-8 - Quinoxaline derivatives as antiparasitic drugs: proof of concept, BP.PD; 14/22548-0 - Quinoxaline derivatives as antiparasitic drugs: proof of concept, BP.PD

Abstract

Quinoxalines are a class of heterocyclic compounds that have been intensively studied for their biological activities, showing promising activity against protozoa, in an ongoing study towards the discovery of new antiparasitic compounds, we have synthesized a library of quinoxaline derivatives, which has been evaluated in vitro against epimastigote, promastigote, and trypomastigote forms of Trypanossoma cruzi and intracellular amastigote and promastigote forms of Leishmania amazonensis. From this screening, we have selected the most active compounds for in vivo and mechanistic studies. The main objective of this project is to prove the biological activity of these compounds in the drug development for tropical diseases such as Chagas' disease and leishmaniasis. More specifically, our goal is the synthesis of quinoxaline derivatives aiming at improving yield, a scalable and safe process and decreasing of chemical residues. Looking into pharmaceutical application of these drug candidates, they will be evaluated in vitro and in vivo in order to determine their mechanism of action against T. cruzi and L. amazonensis. (AU)

Scientific publications

(4)

(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)

SANGI, DIEGO P.; COMINETTI, MARCIA R.; BECCENERI, AMANDA B.; RESENDE, FLAVIA A.; VARANDA, ELIANA A.; MONTANARI, CARLOS A.; PAIXAO, MARCIO W.; CORREA, ARLENE G.. Molecular Design, Synthesis and Evaluation of 2,3-Diarylquinoxalines as Estrogen Receptor Ligands. Medicinal Chemistry, v. 11, n. 8, p. 736-746, 2015. (13/07600-3, 11/01893-3, 13/50680-8)

COGO, JULIANA; CANTIZANI, JUAN; COTILLO, IGNACIO; SANGI, DIEGO PEREIRA; CORREA, ARLENE GONCALVES; UEDA-NAKAMURA, TANIA; DIAS FILHO, BENEDITO PRADO; JULIO MARTIN, JOSE; NAKAMURA, CELSO VATARU. Quinoxaline derivatives as potential antitrypanosomal and antileishmanial agents. Bioorganic & Medicinal Chemistry, v. 26, n. 14, p. 4065-4072, AUG 7 2018. (14/50249-8, 13/07600-3, 13/50680-8)

CORREA, ARLENE G.; PAIXAO, MARCIO W.; SCHWAB, RICARDO S.. Application of Bio-Based Solvents in Catalysis. CURRENT ORGANIC SYNTHESIS, v. 12, n. 6, p. 675-695, 2015. (13/50680-8, 13/06558-3)

RODRIGUES, MARILI V. N.; BARBOSA, ALEXANDRE F.; DA SILVA, JULIA F.; DOS SANTOS, DEBORAH A.; VANZOLINI, KENIA L.; DE MORAES, MARCELA C.; CORREA, ARLENE G.; CASS, QUEZIA B.. 9-Benzoyl 9-deazaguanines as potent xanthine oxidase inhibitors. Bioorganic & Medicinal Chemistry, v. 24, n. 2, p. 226-231, JAN 15 2016. (13/01710-1, 13/50680-8, 13/07600-3)