title: Synthesis, characterization and antitumoral activity of new cobalt(II)complexes: Effect of the ligand isomerism on the biological activity of the complexes.
abstract: The synthesis, physico-chemical characterization and cytotoxicity against five human tumoral cell lines (THP-1, U937, Molt-4, Colo205 and H460) of three new cobalt(II) coordination compounds are reported (i.e. Co(HL1)Cl (1), Co(HL2)Cl (2) and [Co(HL3)Cl]0.0.5 (CH3)2CHOH (3)). H2L2 (2-{[[2-hydroxy-3-(1-naphthyloxy)propyl](pyridin-2-ylmethyl)amino]methyl}phenol) and H2L3 (2-{[[2-hydroxy-3-(2-naphthyloxy)propyl](pyridin-2-ylmethyl)amino]methyl}phenol) present α and β-naphthyl groups respectively, which is absent in H2L1 (N-(2-hydroxybenzyl)-N-(2-pyridylmethyl)[(3-chloro)(2-hydroxy)]propylamine. These compounds were characterized by a range of physico-chemical methods. X-ray diffraction studies were performed for complex (3), indicating the formation of a mononuclear complex. Complexes (2) and (3), which contain α and β-naphthyl groups respectively, have presented lower IC50 values than those exhibited by complex (1). Complex (3) presents IC50 values lower than cisplatin against Colo205 (90 and 196μmolL(-1), respectively) and H460 (147 and 197μmolL(-1), respectively). These human neoplastic cells under investigation were also more susceptible toward complex (3) than peripheral blood mononuclear cells. Transmission electron microscopy investigations are in agreement with the loss of mitochondrial membrane potential (ΔΨm) observed by JC-1 mitochondrial potential sensor and indicate that the activity of complex (3) against leukemic cell line (U937) is mediated by an apoptotic mechanism associated with mitochondrial dysfunction (intrinsic pathway).
authors.affiliation: Laboratório de Ciências Químicas, Universidade Estadual do Norte Fluminense Darcy Ribeiro, 28013-602 Campos dos Goytacazes, RJ, Brazil.
authors.forename: Samila R
authors.initials: SR
authors.lastname: Morcelli
authors.affiliation: Laboratório de Ciências Químicas, Universidade Estadual do Norte Fluminense Darcy Ribeiro, 28013-602 Campos dos Goytacazes, RJ, Brazil.
authors.forename: Érika S
authors.initials: ÉS
authors.lastname: Bull
authors.affiliation: Laboratório de Ciências Químicas, Universidade Estadual do Norte Fluminense Darcy Ribeiro, 28013-602 Campos dos Goytacazes, RJ, Brazil.
authors.forename: Wagner S
authors.initials: WS
authors.lastname: Terra
authors.affiliation: Laboratório de Ciências Químicas, Universidade Estadual do Norte Fluminense Darcy Ribeiro, 28013-602 Campos dos Goytacazes, RJ, Brazil. Electronic address: chrisf@uenf.br.
authors.forename: Rafaela O
authors.initials: RO
authors.lastname: Moreira
authors.affiliation: Instituto Federal Fluminense, 28030-130 Campos dos Goytacazes, RJ, Brazil.
authors.forename: Franz V
authors.initials: FV
authors.lastname: Borges
authors.affiliation: Laboratório de Biologia do Reconhecer, Universidade Estadual do Norte Fluminense Darcy Ribeiro, 28013-602 Campos dos Goytacazes, RJ, Brazil.
authors.forename: Milton M
authors.initials: MM
authors.lastname: Kanashiro
authors.affiliation: Departamento de Química, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, Brazil.
authors.forename: Adailton J
authors.initials: AJ
authors.lastname: Bortoluzzi
authors.affiliation: Laboratório de Fisiologia e Bioquímica de Microorganismos, Universidade Estadual do Norte Fluminense Darcy Ribeiro, 28013-602 Campos dos Goytacazes, RJ, Brazil.
authors.forename: Leide L F
authors.initials: LL
authors.lastname: Maciel
authors.affiliation: Laboratório de Fisiologia e Bioquímica de Microorganismos, Universidade Estadual do Norte Fluminense Darcy Ribeiro, 28013-602 Campos dos Goytacazes, RJ, Brazil.
authors.forename: João Carlos
authors.initials: JC
authors.lastname: de A Almeida
authors.affiliation: Laboratório de Ciências Químicas, Universidade Estadual do Norte Fluminense Darcy Ribeiro, 28013-602 Campos dos Goytacazes, RJ, Brazil.
authors.forename: Adolfo Horn
authors.initials: AH
authors.lastname: Júnior
authors.affiliation: Laboratório de Ciências Químicas, Universidade Estadual do Norte Fluminense Darcy Ribeiro, 28013-602 Campos dos Goytacazes, RJ, Brazil.
authors.forename: Christiane
authors.initials: C
authors.lastname: Fernandes
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D003035:Cobalt / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020298:U937 Cells
chemical_list: D000970:Antineoplastic Agents; D003035:Cobalt
keywords: Antitumoral activity; Cobalt(II); Isomerism; Mononuclear complexes; Transmission electron microscopy (TEM); X-ray