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
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...
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Frontiers Media S.A.
2018-07-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2018.01432/full |
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| author | Pauraic McCarron Pauraic McCarron Malachy McCann Michael Devereux Kevin Kavanagh Ciaran Skerry Petros C. Karakousis Ana C. Aor Thaís P. Mello André L. S. Santos Débora L. Campos Fernando R. Pavan |
| author_facet | Pauraic McCarron Pauraic McCarron Malachy McCann Michael Devereux Kevin Kavanagh Ciaran Skerry Petros C. Karakousis Ana C. Aor Thaís P. Mello André L. S. Santos Débora L. Campos Fernando R. Pavan |
| author_sort | Pauraic McCarron |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-14T03:20:46Z |
| format | Article |
| id | doaj.art-5f4c72292eb843b38dcc1e79d8775504 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-04-14T03:20:46Z |
| publishDate | 2018-07-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-5f4c72292eb843b38dcc1e79d87755042022-12-22T02:15:19ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-07-01910.3389/fmicb.2018.01432382255Unprecedented 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) AnalogsPauraic McCarron0Pauraic McCarron1Malachy McCann2Michael Devereux3Kevin Kavanagh4Ciaran Skerry5Petros C. Karakousis6Ana C. Aor7Thaís P. Mello8André L. S. Santos9Débora L. Campos10Fernando R. Pavan11Chemistry Department, Maynooth University, National University of Ireland, Maynooth, IrelandThe Center for Biomimetic and Therapeutic Research, Focas Research Institute, Dublin Institute of Technology, Dublin, IrelandChemistry Department, Maynooth University, National University of Ireland, Maynooth, IrelandThe Center for Biomimetic and Therapeutic Research, Focas Research Institute, Dublin Institute of Technology, Dublin, IrelandBiology Department, Maynooth University, National University of Ireland, Maynooth, IrelandDivision of Infectious Diseases, Center for Tuberculosis Research, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, United StatesDivision of Infectious Diseases, Center for Tuberculosis Research, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, United StatesDepartamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilDepartamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilDepartamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro, Rio de Janeiro, BrazilFaculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, São Paulo, BrazilFaculdade de Ciências Farmacêuticas, Universidade Estadual Paulista, Araraquara, São Paulo, BrazilMycobacterium 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.https://www.frontiersin.org/article/10.3389/fmicb.2018.01432/fullMycobacterium tuberculosismanganese(II)110-phenanthrolinemetal-based complexantimicrobial agent |
| spellingShingle | Pauraic McCarron Pauraic McCarron Malachy McCann Michael Devereux Kevin Kavanagh Ciaran Skerry Petros C. Karakousis Ana C. Aor Thaís P. Mello André L. S. Santos Débora L. Campos Fernando R. Pavan 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 Mycobacterium tuberculosis manganese(II) 1 10-phenanthroline metal-based complex antimicrobial agent |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Mycobacterium tuberculosis manganese(II) 1 10-phenanthroline metal-based complex antimicrobial agent |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2018.01432/full |
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