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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.)

2,3,8-Trisubstituted Quinolines with Antimalarial Activity

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Author(s):
Martinez, Pablo D. G. [1] ; Krake, Susann H. [1] ; Poggi, Maitia L. [1] ; Campbell, Simon F. [2] ; Willis, Paul A. [2] ; Dias, Luiz C. [1]
Total Authors: 6
Affiliation:
[1] Univ Estadual Campinas, Inst Quim, Caixa Postal 6154, BR-13083970 Campinas, SP - Brazil
[2] ICC, Med Malaria Venture, Route Pre Bois 20, POB 1826, CH-1215 Geneva - Switzerland
Total Affiliations: 2
Document type: Journal article
Source: Anais da Academia Brasileira de Ciências; v. 90, n. 2, p. 1215-1231, 2018.
Web of Science Citations: 1
Abstract

Combination therapy drugs are considered a fundamental way to control malaria as it mimimizes the risk of emergence of resistance to the individual partner drugs. Consequently, this type of therapy constitutes a driving force for the discovery of new drugs with different modes of action, since this will provide options for combining different drugs to achieve the optimum antimalarial treatment. In this context, a 2,3,8-trisubstitued quinoline compound was found in a high throughput screen (HTS) to show an excellent inhibition of P. falciparum NF54 (IC50 = 22 nM) and low cytotoxicity. We performed a detailed evaluation of the substituents to improve the metabolic stability and solubility liabilities of the original hit and identified derivatives with enhanced physicochemical and/or PK properties and that maintained biological activity. However the high potency was not retained on testing against drug resistant plasmodium strains. (AU)

FAPESP's process: 13/07600-3 - CIBFar - Center for Innovation in Biodiversity and Drug Discovery
Grantee:Glaucius Oliva
Support type: Research Grants - Research, Innovation and Dissemination Centers - RIDC
FAPESP's process: 15/50655-9 - FAPESP/MMV/DNDi/UNICAMP/USP Consortium to discover new drugs for the treatment of tropical parasitic diseases
Grantee:Luiz Carlos Dias
Support type: Research Grants - Research Partnership for Technological Innovation - PITE