Sophoradiol inhibits the growth of drug resistant Mycobacterium tuberculosis in vitro and murine models of tuberculosis

Microb Pathog. 2020 Apr:141:103971. doi: 10.1016/j.micpath.2020.103971. Epub 2020 Jan 7.

Abstract

Tuberculosis is a devastating disease responsible for approximately 1.5 million deaths annually especially in developing countries. Although there is recommended and standard treatment for tuberculosis but the non-adherence of the patients to the lengthy treatment, adverse effects of the drugs and the emergence of multi-drug resistant strains hurdles the management of this devastating disease. This study examined the anti-mycobacterial activity of a plant derived triterpenoid, sophoradiol, against the drug-resistant strains of Mycobacterium tuberculosis and also in murine model of tuberculosis. The results showed that sophoradiol exhibits remarkable activity against the H37RV strain with an MIC of 8.5 μg/mL. The MIC of sophoradiol against the drug resistant strains of M. tuberculosis (CX1 to CX5) ranged from 9 to 16 μg/mL. Additionally, sophoradiol exhibited a bactericidal activity against H37RV strain with MBC equal to 2X MIC. Drug interaction studies showed that sophoradiol exhibits additive interaction with isoniazid and synergistic interaction with rifampicin. In the mice model of tuberculosis, sophoradiol also exhibited remarkable efficacy. Finally, cytotoxicity assays showed that sophoradiol exhibits negligible toxicity against the normal human breast cell lines. Taken together, it is concluded that sophoradiol may prove beneficial lead molecule for the management of tuberculosis.

Keywords: Drug resistance; Mycobacterium; Sophoradiol; Triterpenoids; Tuberculosis.

MeSH terms

  • Animals
  • Antitubercular Agents / pharmacology*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Mice
  • Microbial Sensitivity Tests
  • Mycobacterium tuberculosis / drug effects*
  • Oleanolic Acid / analogs & derivatives*
  • Oleanolic Acid / pharmacology
  • Tuberculosis / drug therapy
  • Tuberculosis / microbiology*
  • Tuberculosis, Multidrug-Resistant

Substances

  • Antitubercular Agents
  • sophoradiol
  • Oleanolic Acid