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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

rowth-inhibitory effects of tris-(1,10-phenanthroline) iron (II) against Mycobacterium tuberculosis in vitro and in viv

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Solcia, Mariana Cristina [1] ; Campos, Debora Leite [1] ; Grecco, Julia Araujo [1] ; Paiva Silva, Caio Sander [1] ; da Silva, Patricia Bento [1] ; da Silva, Isabel Cristiane [1] ; Balduino da Silva, Ana Paula [1] ; Silva, Joas [1] ; Oda, Fernando Bombarda [2] ; dos Santos, Andre Gonzaga [2] ; Pavan, Fernando Rogerio [1]
Total Authors: 11
Affiliation:
[1] Sao Paulo State Univ, UNESP, Sch Pharmaceut Sci, TB Res Lab, BR-14800903 Araraquara, SP - Brazil
[2] Sao Paulo State Univ, Sch Pharmaceut Sci, Dept Drugs & Med, UNESP, BR-14800903 Araraquara, SP - Brazil
Total Affiliations: 2
Document type: Journal article
Source: TUBERCULOSIS; v. 128, MAY 2021.
Web of Science Citations: 0
Abstract

Mycobacterium tuberculosis is the major etiological agent for tuberculosis (TB), which is the leading cause of single pathogen infection-related deaths worldwide. The End TB Strategy of the World Health Organization aimed to decrease the incidence of TB by 20% between 2015 and 2020, which was not achieved. Here, the growth-inhibitory effects of tris-(1,10-phenanthroline) iron (II) complex ({[}Fe(phen)(3)](2+)), a known commercially available cheap chemical substance, were examined. The best in vitro results showed great activity with MIC ranging from 0.77 to 3.06 mu M against clinical strains and at low pH (mimicking the granuloma) with MIC of 0.21 mu M. Preliminary safety analysis revealed that the complex did not exhibit cytotoxic activity against different cell lines or mutagenic activity in vitro. The complex was orally bioavailable after 2 h of administration in vivo. Additionally, the results of the acute toxicity test revealed that the complex did not exert toxic effects in female BALB/c mice. The mechanism of action was performed using D29 mycobacteriophages where the treatment with different concentrations of the complex inhibited viral protein synthesis, which indicated that the anti-TB mechanisms of the complex involve protein synthesis inhibition. These findings suggested that {[}Fe(phen)(3)](2+) is a potential novel therapeutic for TB. (AU)

FAPESP's process: 20/13497-4 - Search for the mechanism of action and therapeutic effect of new classes of drugs against Mycobacterium tuberculosis
Grantee:Fernando Rogério Pavan
Support type: Regular Research Grants
FAPESP's process: 18/12270-6 - Safety assessment of benzofuroxan derivatives with potential use in antitubercular therapy by toxicological and toxigenomic approaches
Grantee:Isabel Cristiane da Silva
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 17/12419-7 - Determination of the frequency of mutations of Mycobacterium tuberculosis against the compound tris-(1.10-phenanthroline)iron(II) and in vivo bioavailability studies
Grantee:Caio Sander Paiva Silva
Support type: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 16/24633-0 - Study of the biological profile of tris-(1,10-phenanthroline) iron (II) complex and possible mechanisms of action against Mycobacterium tuberculosis
Grantee:Mariana Cristina Solcia
Support type: Scholarships in Brazil - Master
FAPESP's process: 18/21778-3 - Analysis of in vitro, in vivo and mechanism of action of benzofuroxan compounds against Mycobacterium tuberculosis
Grantee:Debora Leite Campos
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 18/12135-1 - Efflux pumps as a possible mechanism of resistance to 2nd line drugs: phenotypic and genotypic evaluation in resistant clinical isolates of Mycobacterium tuberculosis
Grantee:Júlia Araújo Grecco
Support type: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 18/00163-0 - Development and search of new antimicrobials against Tuberculosis: from screening to pre-clinical studies in vivo
Grantee:Fernando Rogério Pavan
Support type: Regular Research Grants