Manganese(II) complexes with thiosemicarbazones as potential anti-Mycobacterium tuberculosis agents

• The anti-Mycobacterium tuberculosis (MTB) activity of Mn(II) complexes is probed.
• The Mn(II) compounds present two reversible redox processes in the voltammetry.
• DFT calculations are compared with experimental data.
• The complexes show low in vitro cytotoxicity against VERO and J774A.1 cells.
• A promising candidate for tuberculosis treatment is identified.

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-R1 − 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.

Thiosemicarbazone manganese(II) complexes of the type [Mn(atc-R)2] (Hatc-R = 2-acetylpyridine-N(4)-R-thiosemicarbazone) were investigated by several techniques. The high activities against Mycobacterium tuberculosis (MTB) and low in vitro cytotoxicity to VERO and J774 cells presented by these complexes place them on the rank of potential anti-tuberculosis drug candidates.Figure optionsDownload as PowerPoint slide