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<p>Infections by <i>Mycobacterium</i> spp. are responsible for thousands of deaths every year worldwide. Microbial resistance, toxic effects, and adverse consequences of conventional therapies bring forth the need to search for new therapeutic agents. The aim of this study was to determine the antimicrobial action of the molecule Rottlerin against <i>Mycobacterium</i> spp. The broth microdilution assay showed that Rottlerin inhibited the mycobacterial growth at concentrations ≤ 50&#xa0;µg/mL (≤ 96.81&#xa0;µM), and the lowest bactericidal concentration was observed against <i>M. tuberculosis</i> (25&#xa0;µg/mL—48.40&#xa0;µM). The cytotoxicity of Rottlerin was conducted in a epithelial cell culture and evaluated through 2,3-Bis-(2-Methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) colorimetric assay, revealing an IC<sub>50</sub> equivalent to 81.89 ± 4.64&#xa0;µM. The antioxidant action determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay demonstrated that Rottlerin reduced at least 50% of free radicals at 109.2&#xa0;µM. To gain insights into the antimycobacterial activity of Rottlerin, we performed molecular docking simulations with therapeutic targets of <i>M. tuberculosis</i> and observed that Rottlerin binds into the inhibitory site of the anti-infective target diterpene synthase (Rv3378c). Our findings indicate that Rottlerin presents antimicrobial effects with antioxidant action and prominent therapeutic targets, showing its biotechnological potential for the development of new agent against <i>Mycobacterium</i> spp. infection.</p>

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Determining the Antimycobacterial Action of Rottlerin Against Mycobacterium Species and Toxicity, Antioxidant Properties, and Therapeutic Target Affinity of Rottlerin

  • 期刊论文

  • 发表日期：

    2025年2月21日

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  • Jaqueline Lopes Damasceno,
  • Mariana Brentini Santiago,
  • Ralciane de Paula Menezes,
  • Tábata Rodrigues Esperandim,
  • Saulo Duarte Ozelin,
  • Marília Vitória Franco da Silva,
  • Uriel Rodrigues Landaeta,
  • Denise Crispim Tavares,
  • Luis Carlos Scalon Cunha,
  • Eloísa Amália Vieira Ferro,
  • Thales Alves de Melo Fernandes,
  • Carlos Henrique Gomes Martins

摘要

Infections by Mycobacterium spp. are responsible for thousands of deaths every year worldwide. Microbial resistance, toxic effects, and adverse consequences of conventional therapies bring forth the need to search for new therapeutic agents. The aim of this study was to determine the antimicrobial action of the molecule Rottlerin against Mycobacterium spp. The broth microdilution assay showed that Rottlerin inhibited the mycobacterial growth at concentrations ≤ 50 µg/mL (≤ 96.81 µM), and the lowest bactericidal concentration was observed against M. tuberculosis (25 µg/mL—48.40 µM). The cytotoxicity of Rottlerin was conducted in a epithelial cell culture and evaluated through 2,3-Bis-(2-Methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) colorimetric assay, revealing an IC50 equivalent to 81.89 ± 4.64 µM. The antioxidant action determined by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay demonstrated that Rottlerin reduced at least 50% of free radicals at 109.2 µM. To gain insights into the antimycobacterial activity of Rottlerin, we performed molecular docking simulations with therapeutic targets of M. tuberculosis and observed that Rottlerin binds into the inhibitory site of the anti-infective target diterpene synthase (Rv3378c). Our findings indicate that Rottlerin presents antimicrobial effects with antioxidant action and prominent therapeutic targets, showing its biotechnological potential for the development of new agent against Mycobacterium spp. infection.