title: Bismuth(III) complexes with 2-acetylpyridine- and 2-benzoylpyridine-derived hydrazones: Antimicrobial and cytotoxic activities and effects on the clonogenic survival of human solid tumor cells.
abstract: Complexes [Bi(2AcPh)Cl2]·0.5H2O (1), [Bi(2AcpClPh)Cl2] (2), [Bi(2AcpNO2Ph)Cl2] (3), [Bi(2AcpOHPh)Cl2]·2H2O (4), [Bi(H2BzPh)Cl3]·2H2O (5), [Bi(H2BzpClPh)Cl3] (6), [Bi(2BzpNO2Ph)Cl2]·2H2O (7) and [Bi(H2BzpOHPh)Cl3]·2H2O (8) were obtained with 2-acetylpyridine phenylhydrazone (H2AcPh), its -para-chloro-phenyl- (H2AcpClPh), -para-nitro-phenyl (H2AcpNO2Ph) and -para-hydroxy-phenyl (H2AcpOHPh) derivatives, as well as with the 2-benzoylpyridine phenylhydrazone analogues (H2BzPh, H2BzpClPh, H2BzpNO2Ph, H2BzpOHPh). Upon coordination to bismuth(III) antibacterial activity against Gram-positive and Gram-negative bacterial strains significantly improved except for complex (4). The cytotoxic effects of the compounds under study were evaluated on HL-60, Jurkat and THP-1 leukemia, and on MCF-7 and HCT-116 solid tumor cells, as well as on non-malignant Vero cells. In general, 2-acetylpyridine-derived hydrazones proved to be more potent and more selective as cytotoxic agents than the corresponding 2-benzoylpyridine-derived counterparts. Exposure of HCT-116 cells to H2AcpClPh, H2AcpNO2Ph and complex (3) led to 99% decrease of the clonogenic survival. The IC50 values of these compounds were three-fold smaller when cells were cultured in soft-agar (3D) than when cells were cultured in monolayer (2D), suggesting that they constitute interesting scaffolds, which should be considered in further studies aiming to develop new drug candidates for the treatment of colon cancer.
authors.affiliation: Departamento de Química, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Isabella P
authors.initials: IP
authors.lastname: Ferreira
authors.affiliation: Departamento de Química, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Elisa D L
authors.initials: EDL
authors.lastname: Piló
authors.affiliation: Departamento de Química, Universidade Federal de Viçosa, 36570-900 Viçosa, MG, Brazil.
authors.forename: Angel A
authors.initials: AA
authors.lastname: Recio-Despaigne
authors.affiliation: Departamento de Farmácia, Universidade Federal de Juiz de Fora (UFJF), Campus Governador Valadares, 35010-177 Governador Valadares, MG, Brazil.
authors.forename: Jeferson G
authors.initials: JG
authors.lastname: Da Silva
authors.affiliation: Departamento de Fisiologia, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Jonas P
authors.initials: JP
authors.lastname: Ramos
authors.affiliation: Departamento de Fisiologia, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Lucas B
authors.initials: LB
authors.lastname: Marques
authors.affiliation: Departamento de Fisiologia, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Pedro H D M
authors.initials: PHDM
authors.lastname: Prazeres
authors.affiliation: Departamento de Química, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Jacqueline A
authors.initials: JA
authors.lastname: Takahashi
authors.affiliation: Departamento de Fisiologia, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Souza-Fagundes
authors.affiliation: Departamento de Química, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil.
authors.forename: Willian
authors.initials: W
authors.lastname: Rocha
authors.affiliation: Departamento de Química, Universidade Federal de Minas Gerais, 31270-901 Belo Horizonte, MG, Brazil. Electronic address: hberaldo@ufmg.br.
authors.forename: Heloisa
authors.initials: H
authors.lastname: Beraldo
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D001419:Bacteria / Q000187:drug effects*; D001729:Bismuth / Q000737:chemistry*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D003114:Colony-Forming Units Assay; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity*; D006801:Humans; D006835:Hydrazones / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D009369:Neoplasms / Q000188:drug therapy; D011725:Pyridines / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014709:Vero Cells
chemical_list: D000890:Anti-Infective Agents; D056831:Coordination Complexes; D006835:Hydrazones; D011725:Pyridines; C543930:2-acetylpyridine; D001729:Bismuth
keywords: 2-Acetylpyridinephenyl hydrazones; 2-Benzoylpyridinephenyl hydrazones; Antibacterial activity; Bismuth(III) complexes; Clonogenic survival; Cytotoxic activity