Anti-Plasmodium falciparum activity of quinoline-sulfonamide hybrids

Luiz C S Pinheiro; Núbia Boechat; Maria de Lourdes G Ferreira; Carlos C S Júnior; Antônio M L Jesus; Milene M M Leite; Nicolli B Souza; Antoniana U Krettli

doi:10.1016/j.bmc.2015.06.056

Anti-Plasmodium falciparum activity of quinoline-sulfonamide hybrids

Bioorg Med Chem. 2015 Sep 1;23(17):5979-84. doi: 10.1016/j.bmc.2015.06.056. Epub 2015 Jul 2.

Authors

Luiz C S Pinheiro¹, Núbia Boechat², Maria de Lourdes G Ferreira¹, Carlos C S Júnior³, Antônio M L Jesus¹, Milene M M Leite¹, Nicolli B Souza⁴, Antoniana U Krettli⁵

Affiliations

¹ Departamento de Síntese de Fármacos, Instituto de Tecnologia em Fármacos, Farmanguinhos-FIOCRUZ, Rua Sizenando Nabuco 100, Manguinhos, Rio de Janeiro, RJ 21041-250, Brazil.
² Departamento de Síntese de Fármacos, Instituto de Tecnologia em Fármacos, Farmanguinhos-FIOCRUZ, Rua Sizenando Nabuco 100, Manguinhos, Rio de Janeiro, RJ 21041-250, Brazil. Electronic address: boechat@far.fiocruz.br.
³ Departamento de Síntese de Fármacos, Instituto de Tecnologia em Fármacos, Farmanguinhos-FIOCRUZ, Rua Sizenando Nabuco 100, Manguinhos, Rio de Janeiro, RJ 21041-250, Brazil; Programa de Pós Graduação em Farmacologia e Química Medicinal, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
⁴ Centro de Pesquisas René Rachou, CPqRR-FIOCRUZ, Belo Horizonte, MG 30190-002, Brazil.
⁵ Centro de Pesquisas René Rachou, CPqRR-FIOCRUZ, Belo Horizonte, MG 30190-002, Brazil; Programa de Pós Graduação em Medicina Molecular, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil. Electronic address: akrettli@cpqrr.fiocruz.br.

PMID: 26190461
DOI: 10.1016/j.bmc.2015.06.056

Abstract

Fifteen quinoline-sulfonamide hybrids, with a 7-chloroquinoline moiety connected by a linker group to arylsulfonamide moieties with different substituents in the 4-position were synthesized and assayed against Plasmodium falciparum. The compounds displayed high schizonticidal blood activity in vitro, with IC50 values ranging from 0.05 to 1.63 μM, in the anti-HPR2 assay against clone W2-chloroquine-resistant; ten of them showed an IC50 (ranging from 0.05 to 0.40 μM) lower than that of chloroquine and sulfadoxine. Among them, two compounds inhibited Plasmodium berghei parasitemia by 47% and 49% on day 5 after mice inoculation. The most active, in vivo, hybrid 13 is considered to be a new prototype for the development of an antimalarial drug against chloroquine-resistant parasites.

Keywords: Hybrids; Malaria; Plasmodium falciparum; Quinoline; Sulfonamide.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Humans
Malaria / drug therapy*
Mice
Molecular Structure
Plasmodium falciparum / drug effects*
Quinolines / therapeutic use*
Sulfonamides / therapeutic use

Substances

Quinolines
Sulfonamides
quinoline