title: Manganese(II) complexes with thiosemicarbazones as potential anti-Mycobacterium tuberculosis agents.
abstract: Through a systematic variation on the structure of a series of manganese complexes derived from 2-acetylpyridine-N(4)-R-thiosemicarbazones (Hatc-R), structural features have been investigated with the aim of obtaining complexes with potent anti-Mycobacterium tuberculosis activity. The analytical methods used for characterization included FTIR, EPR, UV-visible, elemental analysis, cyclic voltammetry, magnetic susceptibility measurement and single crystal X-ray diffractometry. Density functional theory (DFT) calculations were performed in order to evaluate the contribution of the thiosemicarbazonate ligands on the charge distribution of the complexes by changing the peripheral groups as well as to verify the Mn-donor atoms bond dissociation predisposition. The results obtained are consistent with the monoanionic N,N,S-tridentate coordination of the thiosemicarbazone ligands, resulting in octahedral complexes of the type [Mn(atc-R)2], paramagnetic in the extension of 5 unpaired electrons, whose EPR spectra are consistent for manganese(II). The electrochemical analyses show two nearly reversible processes, which are influenced by the peripheral substituent groups at the N4 position of the atc-R(1-) ligands. The minimal inhibitory concentration (MIC) of these compounds against M. tuberculosis as well as their in vitro cytotoxicity on VERO and J774A.1 cells (IC50) was determined in order to find their selectivity index (SI) (SI=IC50/MIC). The results evidenced that the compounds described here can be considered as promising anti-M. tuberculosis agents, with SI values comparable or better than some commercial drugs available for the tuberculosis treatment.
authors.affiliation: Instituto de Química de São Carlos, Universidade de São Paulo, 13566-590 São Carlos, SP, Brazil.
authors.forename: Carolina G
authors.initials: CG
authors.lastname: Oliveira
authors.affiliation: Departamento de Química, Universidade Federal do Triângulo Mineiro, 38025-440 Uberaba, MG, Brazil.
authors.forename: Pedro Ivo
authors.initials: PI
authors.lastname: da S Maia
authors.affiliation: Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, 14801-902 Araraquara, SP, Brazil.
authors.forename: Paula C
authors.initials: PC
authors.lastname: Souza
authors.affiliation: Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, 14801-902 Araraquara, SP, Brazil.
authors.forename: Fernando R
authors.initials: FR
authors.lastname: Pavan
authors.affiliation: Faculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, 14801-902 Araraquara, SP, Brazil.
authors.forename: Clarice Q F
authors.initials: CQ
authors.lastname: Leite
authors.affiliation: Instituto de Química de São Carlos, Universidade de São Paulo, 13566-590 São Carlos, SP, Brazil.
authors.forename: Rommel B
authors.initials: RB
authors.lastname: Viana
authors.affiliation: Departamento de Química, Universidade Federal de São Carlos, 13565-905 São Carlos, SP, Brazil.
authors.forename: Alzir A
authors.initials: AA
authors.lastname: Batista
authors.affiliation: Instituto de Física de São Carlos, Universidade de São Paulo, CP 369, 13560-970 São Carlos, SP, Brazil.
authors.forename: Otaciro R
authors.initials: OR
authors.lastname: Nascimento
authors.affiliation: Instituto de Química de São Carlos, Universidade de São Paulo, 13566-590 São Carlos, SP, Brazil. Electronic address: deflon@iqsc.usp.br.
authors.forename: Victor M
authors.initials: VM
authors.lastname: Deflon
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D002522:Chlorocebus aethiops; D018360:Crystallography, X-Ray; D008345:Manganese / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013882:Thiosemicarbazones / Q000737:chemistry* / Q000494:pharmacology*; D014709:Vero Cells
chemical_list: D000900:Anti-Bacterial Agents; D013882:Thiosemicarbazones; D008345:Manganese
keywords: Anti-Mycobacterium tuberculosis activity; Catalase peroxidase; Manganese(II); Thiosemicarbazones