Unprecedented in Vitro Antitubercular Activitiy of Manganese(II) Complexes Containing 1,10- Phenanthroline and Dicarboxylate Ligands: Increased Activity, Superior Selectivity, and Lower Toxicity in Comparison to Their Copper(II) Analogs

Authors

Pauraic McCarron, Maynooth University, Department of Chemistry, Maynooth, IrelandFollow
Malachy McCann, Maynooth University, Department of Chemistry, Maynooth, Ireland
Michael Devereux, Technological University DublinFollow
Kevin Kavanagh, Maynooth University, Department of Biology, Maynooth, Ireland
Ciaran M. Skerry, The Johns Hopkins School of Medicine, Department of Medicine, Baltimore, United States
Petros C. Karakousis, The Johns Hopkins School of Medicine, Baltimore, United States
Ana Carolina Aor, Universidade Federal do Rio de Janeiro, Departamento de Microbiologia Geral, Rio de Janeiro, Brazil
Thaís P. Mello, Universidade Federal do Rio de Janeiro, Departamento de Microbiologia Geral, Rio de Janeiro, Brazil
Dos Santos, André Luis Souza Dos Santos, André Luis Souza, Universidade Federal do Rio de Janeiro, Departamento de Microbiologia Geral, Rio de Janeiro, Brazil
Débora Leite Campos, UNESP-Universidade Estadual Paulista, Department of Biological Sciences, Sao Paulo, Brazil
Fernando R. Pavan, UNESP-Universidade Estadual Paulista, Department of Biological Sciences, Sao Paulo, Brazil

Document Type

Article

Rights

Available under a Creative Commons Attribution Non-Commercial Share Alike 4.0 International Licence

Disciplines

Microbiology

Publication Details

Frontiers in Microbiology, Volume 9, Issue JUL, 2 July 2018, Article number 1432

Abstract

Mycobacterium tuberculosis is the etiologic agent of tuberculosis. The demand for new chemotherapeutics with unique mechanisms of action to treat (multi)resistant strains is an urgent need. The objective of this work was to test the effect of manganese(II) and copper(II) phenanthroline/dicarboxylate complexes against M. tuberculosis. The water-soluble Mn(II) complexes, [Mn2(oda)(phen)4(H2O)2][Mn2(oda)(phen)4(oda)2]·4H2O (1) and ([Mn(3,6,9-tdda)(phen)2]·3H2O·EtOH)n (3) (odaH2 = octanedioic acid, phen = 1,10-phenanthroline, tddaH2 = 3,6,9-trioxaundecanedioic acid), and water-insoluble complexes, [Mn(ph)(phen)(H2O)2] (5), [Mn(ph)(phen)2(H2O)]·4H2O (6), [Mn2(isoph)2(phen)3]·4H2O (7), ([Mn(phen)2(H2O)2])2(isoph)2(phen)·12H2O (8) and [Mn(tereph)(phen)2]·5H2O (9) (phH2 = phthalic acid, isophH2 = isophthalic acid, terephH2 = terephthalic acid), robustly inhibited the viability of M. tuberculosis strains, H37Rv and CDC1551. The water-soluble Cu(II) analog of (1), [Cu2(oda)(phen)4](ClO4)2·2.76H2O·EtOH (2), was significantly less effective against both strains. Whilst (3) retarded H37Rv growth much better than its soluble Cu(II) equivalent, ([Cu(3,6,9-tdda)(phen)2]·3H2O·EtOH)n (4), both were equally efficient against CDC1551. VERO and A549 mammalian cells were highly tolerant to the Mn(II) complexes, culminating in high selectivity index (SI) values. Significantly, in vivo studies using Galleria mellonella larvae indicated that the metal complexes were minimally toxic to the larvae. The Mn(II) complexes presented low MICs and high SI values (up to 1347), indicating their auspicious potential as novel antitubercular lead agents. © 2018 McCarron, McCann, Devereux, Kavanagh, Skerry, Karakousis, Aor, Mello, Santos, Campos and Pavan.

DOI

https://doi.org/10.3389/fmicb.2018.01432

Recommended Citation

McCarron, P., McCann M. & Devereux, M. (2018). Unprecedented in Vitro Antitubercular Activitiy of Manganese(II) Complexes Containing 1,10- Phenanthroline and Dicarboxylate Ligands: Increased Activity, Superior Selectivity, and Lower Toxicity in Comparison to Their Copper(II) Analogs. Frontiers in Microbiology, vol. 9, no. 2 July 2018, 2018, Article number 1432. doi:10.3389/fmicb.2018.01432