title: Synthesis, cytotoxicity and mechanistic evaluation of 4-oxoquinoline-3-carboxamide derivatives: finding new potential anticancer drugs.
abstract: 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.
authors.affiliation: Outeiro de São João Batista, Fluminense FederalUniversity (UFF), s/n, Niterói 24020141, RJ, Brazil.
authors.forename: Luana da S M
authors.initials: Lda S
authors.lastname: Forezi
authors.affiliation: Outeiro de São João Batista, Fluminense FederalUniversity (UFF), s/n, Niterói 24020141, RJ, Brazil.
authors.forename: Nathalia M C
authors.initials: NM
authors.lastname: Tolentino
authors.affiliation: Laboratory of Molecular Modeling & QSAR (ModMolQSAR), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21949-900, RJ, Brazil.
authors.forename: Alessandra M T
authors.initials: AM
authors.lastname: de Souza
authors.affiliation: LABIEMol, Outeiro de São João Batista, Fluminense Federal University, s/n, Niterói 24020-141, RJ, Brazil.
authors.forename: Helena C
authors.initials: HC
authors.lastname: Castro
authors.affiliation: Institute of Biological Sciences, Federal University of Pará, Av. Augusto Corrêa, n.01-Guamá, Belém, 66075-110, Pará, Brazil.
authors.forename: Raquel C
authors.initials: RC
authors.lastname: Montenegro
authors.affiliation: Laboratory of Biochemistry of Proteins and Peptides, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro 21040-900, RJ, Brazil.
authors.forename: Rafael F
authors.initials: RF
authors.lastname: Dantas
authors.affiliation: Laboratory of Biochemistry of Proteins and Peptides, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro 21040-900, RJ, Brazil.
authors.forename: Maria E I M
authors.initials: ME
authors.lastname: Oliveira
authors.affiliation: Laboratory of Biochemistry of Proteins and Peptides, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro 21040-900, RJ, Brazil.
authors.forename: Floriano P
authors.initials: FP
authors.lastname: Silva
authors.affiliation: Institute of Biological Sciences, Federal University of Pará, Av. Augusto Corrêa, n.01-Guamá, Belém, 66075-110, Pará, Brazil.
authors.forename: Leilane H
authors.initials: LH
authors.lastname: Barreto
authors.affiliation: Institute of Biological Sciences, Federal University of Pará, Av. Augusto Corrêa, n.01-Guamá, Belém, 66075-110, Pará, Brazil.
authors.forename: Rommel M R
authors.initials: RM
authors.lastname: Burbano
authors.affiliation: Laboratory of Molecular Modeling & QSAR (ModMolQSAR), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21949-900, RJ, Brazil.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Abrahim-Vieira
authors.affiliation: Laboratory of Molecular Modeling & QSAR (ModMolQSAR), Federal University of Rio de Janeiro (UFRJ), Rio de Janeiro 21949-900, RJ, Brazil.
authors.forename: Riethe
authors.initials: R
authors.lastname: de Oliveira
authors.affiliation: Outeiro de São João Batista, Fluminense FederalUniversity (UFF), s/n, Niterói 24020141, RJ, Brazil.
authors.forename: Vitor F
authors.initials: VF
authors.lastname: Ferreira
authors.affiliation: Outeiro de São João Batista, Fluminense FederalUniversity (UFF), s/n, Niterói 24020141, RJ, Brazil.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Cunha
authors.affiliation: Outeiro de São João Batista, Fluminense FederalUniversity (UFF), s/n, Niterói 24020141, RJ, Brazil.
authors.forename: Fernanda da C S
authors.initials: Fda C
authors.lastname: Boechat
authors.affiliation: Outeiro de São João Batista, Fluminense FederalUniversity (UFF), s/n, Niterói 24020141, RJ, Brazil. gqocica@vm.uff.br.
authors.forename: Maria Cecília B V
authors.initials: MC
authors.lastname: de Souza
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D003198:Computer Simulation; D004317:Doxorubicin / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004912:Erythrocytes / Q000187:drug effects; D053878:Hemolytic Agents / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D015363:Quinolones / Q000737:chemistry; D013274:Stomach Neoplasms / Q000188:drug therapy
chemical_list: D000970:Antineoplastic Agents; D053878:Hemolytic Agents; D015363:Quinolones; D004317:Doxorubicin