2,3,8-Trisubstituted Quinolines with Antimalarial Activity



Document title: 2,3,8-Trisubstituted Quinolines with Antimalarial Activity
Journal: Anais da Academia Brasileira de Ciencias
Database: PERIÓDICA
System number: 000419774
ISSN: 0001-3765
Authors: 1
1
1
2
2
1
Institutions: 1Universidade Estadual de Campinas, Instituto de Quimica, Campinas, Sao Paulo. Brasil
2Medicines for Malaria Venture, Ginebra. Suiza
Year:
Season: May
Volumen: 90
Number: 1
Pages: 1215-1232
Country: Brasil
Language: Inglés
Document type: Artículo
Approach: Experimental, aplicado
English 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
Disciplines: Medicina,
Química
Keyword: Química farmacéutica,
Quinolinas,
Actividad antimalárica,
Resistencia a fármacos,
Plasmodium falciparum
Keyword: Medicinal chemistry,
Quinolines,
Antimalarial activity,
Drug resistance,
Plasmodium falciparum
Full text: Texto completo (Ver HTML)