Design, synthesis and anti-P. falciparum activity of pyrazolopyridine-sulfonamide derivatives. 2016

Thais B Silva, and Alice M R Bernardino, and Maria de Lourdes G Ferreira, and Kamilla R Rogerio, and Leonardo J M Carvalho, and Nubia Boechat, and Luiz C S Pinheiro
Departamento de Síntese de Fármacos, Instituto de Tecnologia em Fármacos, Farmanguinhos-FIOCRUZ, Fundação Oswaldo Cruz, Rua Sizenando Nabuco 100, Manguinhos, Rio de Janeiro, RJ 21041-250, Brazil; Programa de Pós-Graduação em Química, Departamento de Química Orgânica, Universidade Federal Fluminense, Niterói, RJ, Brazil.

Ten 1-phenyl-1H-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 9.30μM. The most active derivatives with substituent R2=Cl or CH3 at the benzenesulfonamide moiety exhibited the lowest IC50. Compounds with an R1=CO2Et substituent at the 5-position of the 1H-pyrazolo[3,4-b]pyridine ring presented lower activity than those with a CN substituent. The 1H-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.

UI MeSH Term Description Entries
D010963 Plasmodium falciparum A species of protozoa that is the causal agent of falciparum malaria (MALARIA, FALCIPARUM). It is most prevalent in the tropics and subtropics. Plasmodium falciparums,falciparums, Plasmodium
D011720 Pyrazoles Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
D011725 Pyridines Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D000962 Antimalarials Agents used in the treatment of malaria. They are usually classified on the basis of their action against plasmodia at different stages in their life cycle in the human. (From AMA, Drug Evaluations Annual, 1992, p1585) Anti-Malarial,Antimalarial,Antimalarial Agent,Antimalarial Drug,Anti-Malarials,Antimalarial Agents,Antimalarial Drugs,Agent, Antimalarial,Agents, Antimalarial,Anti Malarial,Anti Malarials,Drug, Antimalarial,Drugs, Antimalarial
D013057 Spectrum Analysis The measurement of the amplitude of the components of a complex waveform throughout the frequency range of the waveform. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed) Spectroscopy,Analysis, Spectrum,Spectrometry
D013449 Sulfonamides A group of compounds that contain the structure SO2NH2. Sulfonamide,Sulfonamide Mixture,Sulfonamide Mixtures,Mixture, Sulfonamide,Mixtures, Sulfonamide
D015195 Drug Design The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include PHARMACOKINETICS, dosage analysis, or drug administration analysis. Computer-Aided Drug Design,Computerized Drug Design,Drug Modeling,Pharmaceutical Design,Computer Aided Drug Design,Computer-Aided Drug Designs,Computerized Drug Designs,Design, Pharmaceutical,Drug Design, Computer-Aided,Drug Design, Computerized,Drug Designs,Drug Modelings,Pharmaceutical Designs
D020128 Inhibitory Concentration 50 The concentration of a compound needed to reduce population growth of organisms, including eukaryotic cells, by 50% in vitro. Though often expressed to denote in vitro antibacterial activity, it is also used as a benchmark for cytotoxicity to eukaryotic cells in culture. IC50,Concentration 50, Inhibitory

Related Publications

Thais B Silva, and Alice M R Bernardino, and Maria de Lourdes G Ferreira, and Kamilla R Rogerio, and Leonardo J M Carvalho, and Nubia Boechat, and Luiz C S Pinheiro
June 2021, Molecules (Basel, Switzerland),
Thais B Silva, and Alice M R Bernardino, and Maria de Lourdes G Ferreira, and Kamilla R Rogerio, and Leonardo J M Carvalho, and Nubia Boechat, and Luiz C S Pinheiro
January 2008, Bioorganic & medicinal chemistry letters,
Thais B Silva, and Alice M R Bernardino, and Maria de Lourdes G Ferreira, and Kamilla R Rogerio, and Leonardo J M Carvalho, and Nubia Boechat, and Luiz C S Pinheiro
October 2004, Journal of medicinal chemistry,
Thais B Silva, and Alice M R Bernardino, and Maria de Lourdes G Ferreira, and Kamilla R Rogerio, and Leonardo J M Carvalho, and Nubia Boechat, and Luiz C S Pinheiro
January 2015, European journal of medicinal chemistry,
Thais B Silva, and Alice M R Bernardino, and Maria de Lourdes G Ferreira, and Kamilla R Rogerio, and Leonardo J M Carvalho, and Nubia Boechat, and Luiz C S Pinheiro
September 2015, Bioorganic & medicinal chemistry,
Thais B Silva, and Alice M R Bernardino, and Maria de Lourdes G Ferreira, and Kamilla R Rogerio, and Leonardo J M Carvalho, and Nubia Boechat, and Luiz C S Pinheiro
February 2018, Bioorganic & medicinal chemistry letters,
Thais B Silva, and Alice M R Bernardino, and Maria de Lourdes G Ferreira, and Kamilla R Rogerio, and Leonardo J M Carvalho, and Nubia Boechat, and Luiz C S Pinheiro
October 2016, European journal of medicinal chemistry,
Thais B Silva, and Alice M R Bernardino, and Maria de Lourdes G Ferreira, and Kamilla R Rogerio, and Leonardo J M Carvalho, and Nubia Boechat, and Luiz C S Pinheiro
May 2022, Journal of agricultural and food chemistry,
Thais B Silva, and Alice M R Bernardino, and Maria de Lourdes G Ferreira, and Kamilla R Rogerio, and Leonardo J M Carvalho, and Nubia Boechat, and Luiz C S Pinheiro
December 1996, Farmaco (Societa chimica italiana : 1989),
Thais B Silva, and Alice M R Bernardino, and Maria de Lourdes G Ferreira, and Kamilla R Rogerio, and Leonardo J M Carvalho, and Nubia Boechat, and Luiz C S Pinheiro
October 2022, Chemistry & biodiversity,
Copied contents to your clipboard!