McCarron, Pauraic and McCann, Malachy and Devereux, Michael and Kavanagh, Kevin and Skerry, Ciaran M. and Karakousis, Petros C. and Aor, Ana C. and Mello, Thaís P. and Santos, Andre L. S. and Campos, Débora L. and Pavan, Fernando R. (2018) Unprecedented in Vitro Antitubercular Activity 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, 9 (01432). ISSN 1664-302X

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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.

Item Type:	Article
Additional Information:	Copyright © 2018 McCarron, McCann, Devereux, Kavanagh, Skerry, Karakousis, Aor, Mello, Santos, Campos and Pavan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. Cite as: McCarron P, McCann M, Devereux M, Kavanagh K, Skerry C, Karakousis PC, Aor AC, Mello TP, Santos ALS, Campos DL and Pavan FR (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. Front. Microbiol. 9:1432. doi: 10.3389/fmicb.2018.01432
Keywords:	Mycobacteriumtuberculosis; manganese(II); 1; 10-phenanthroline; metal-based complex; antimicrobial agent; Galleria mellonella;
Academic Unit:	Faculty of Science and Engineering > Biology
Item ID:	11074
Identification Number:	https://doi.org/10.3389/fmicb.2018.01432
Depositing User:	Dr. Kevin Kavanagh
Date Deposited:	23 Sep 2019 13:17
Journal or Publication Title:	Frontiers in Microbiology
Publisher:	Frontiers Media
Refereed:	Yes
URI:	https://www.frontiersin.org
Use Licence:	This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available here

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