Design, synthesis and anti-P. falciparum activity of pyrazolopyridine–sulfonamide derivatives. Issue 18 (15th September 2016)

• Record Type: Journal Article
• Authors: Silva, Thais B.; Bernardino, Alice M.R.; Ferreira, Maria de Lourdes G.; Rogerio, Kamilla R.; Carvalho, Leonardo J.M.; Boechat, Nubia; Pinheiro, Luiz C.S.
• Is Part Of: Bioorganic & medicinal chemistry. Volume 24:Issue 18(2016)
• Page Start: 4492
• Page End: 4498
• Publication Date: 2016-09-15
• Subjects: Malaria -- Pyrazolopyridine -- Sulfonamide -- Plasmodium falciparum; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; Chemistry, Clinical -- Periodicals; Chemistry, Organic -- Periodicals; Chimie bio-organique -- Périodiques; Chimie pharmaceutique -- Périodiques; 615.19
• DOI: 10.1016/j.bmc.2016.07.049
• Languages: English
• ISSNs: 0968-0896

Abstract

Graphical abstract: Abstract: Ten 1-phenyl-1 H -pyrazolo[3, 4- b ]pyridine derivatives connected by a linker group to benzenesulfonamide moieties with different substituents in the 4-position were synthesized and assayed against Plasmodium falciparum . These ten compounds exhibited activity in vitro against the chloroquine-resistant clone W2 with IC50 values ranging from 3.46 to 9.30 μM. The most active derivatives with substituent R2 = Cl or CH3 at the benzenesulfonamide moiety exhibited the lowest IC50 . Compounds with an R1 = CO2 Et substituent at the 5-position of the 1 H -pyrazolo[3, 4- b ]pyridine ring presented lower activity than those with a CN substituent. The 1 H -pyrazolo[3, 4- b ]pyridine system appears to be promising for further studies as an antimalarial for overcoming the burden of resistance in P. falciparum .