| Revista: | Anais da Academia Brasileira de Ciencias |
| Base de datos: | PERIÓDICA |
| Número de sistema: | 000419774 |
| ISSN: | 0001-3765 |
| Autores: | Martinez, Pablo D.G1 Krake, Susann H1 Poggi, Maitia L1 Campbell, Simon F2 Willis, Paul A2 Dias, Luiz C1 |
| Instituciones: | 1Universidade Estadual de Campinas, Instituto de Quimica, Campinas, Sao Paulo. Brasil 2Medicines for Malaria Venture, Ginebra. Suiza |
| Año: | 2018 |
| Periodo: | May |
| Volumen: | 90 |
| Número: | 1 |
| Paginación: | 1215-1232 |
| País: | Brasil |
| Idioma: | Inglés |
| Tipo de documento: | Artículo |
| Enfoque: | Experimental, aplicado |
| Resumen en inglés | 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 |
| Disciplinas: | Medicina, Química |
| Palabras clave: | Química farmacéutica, Quinolinas, Actividad antimalárica, Resistencia a fármacos, Plasmodium falciparum |
| Keyword: | Medicinal chemistry, Quinolines, Antimalarial activity, Drug resistance, Plasmodium falciparum |
| Texto completo: | Texto completo (Ver HTML) |
