Study on the regioselectivity of the N-ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide

4-Oxoquinolines are a class of organic substances of great importance in medicinal chemistry, due to their biological and synthetic versatility. N-1-Alkylated-4-oxoquinoline derivatives have been associated with different pharmacological activities such as antibacterial and antiviral. The presence of a carboxamide unit connected to carbon C-3 of the 4-oxoquinoline core has been associated with various biological activities. Experimentally, the N-ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide occurs at the nitrogen of the oxoquinoline group, in a regiosselective way. In this work, we employed DFT methods to investigate the regiosselective ethylation reaction of N-benzyl-4-oxo-1,4-dihydroquinoline-3-carboxamide, evaluating its acid/base behavior and possible reaction paths

Synthesis, Cytotoxicity and Mechanistic Evaluation of 4-Oxoquinoline-3-carboxamide Derivatives: Finding New Potential Anticancer Drugs

Made available in DSpace on 2015-05-04T16:34:31Z (GMT). No. of bitstreams: 2 license.txt: 1914 bytes, checksum: 7d48279ffeed55da8dfe2f8e81f3b81f (MD5) floriano_silvajretal_IOC_2014.pdf: 1412917 bytes, checksum: efe4a373bbf1ee3722bc9e0e8338d523 (MD5) Previous issue date: 2014Universidade Federal Fluminense. Outeiro de São João Batista. Niterói, Brasil.Universidade Federal Fluminense. Outeiro de São João Batista. Niterói, Brasil.Universidade Federal do Rio de Janeiro. Laboratório de Modelagem Molecular e 3D QSAR (ModMolQSAR). Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense. LABIEMol. Outeiro de São João Batista. Niterói, RJ, Brasil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Belém, PA, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Proteinas e Peptídeos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Proteinas e Peptídeos. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Bioquímica de Proteinas e Peptídeos. Rio de Janeiro, RJ, Brasil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Belém, PA, Brasil.Universidade Federal do Pará. Instituto de Ciências Biológicas. Belém, PA, Brasil.Universidade Federal do Rio de Janeiro. Laboratório de Modelagem Molecular e 3D QSAR (ModMolQSAR). Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Laboratório de Modelagem Molecular e 3D QSAR (ModMolQSAR). Rio de Janeiro, RJ, Brasil.Universidade Federal Fluminense. Outeiro de São João Batista. Niterói, Brasil.Universidade Federal Fluminense. Outeiro de São João Batista. Niterói, Brasil.Universidade Federal Fluminense. Outeiro de São João Batista. Niterói, Brasil.Universidade Federal Fluminense. Outeiro de São João Batista. Niterói, Brasil.As part of a continuing search for new potential anticancer candidates, we describe the synthesis, cytotoxicity and mechanistic evaluation of a series of 4-oxoquinoline-3-carboxamide derivatives as novel anticancer agents. The inhibitory activity of compounds 10–18 was determined against three cancer cell lines using the MTT colorimetric assay. The screening revealed that derivatives 16b and 17b exhibited significant cytotoxic activity against the gastric cancer cell line but was not active against a normal cell line, in contrast to doxorubicin, a standard chemotherapeutic drug in clinical use. Interestingly, no hemolytical activity was observed when the toxicity of 16b and 17b was tested against blood cells. The in silico and in vitro mechanistic evaluation indicated the potential of 16b as a lead for the development of novel anticancer agents against gastric cancer cells