Promising Lead Compounds in the Development of Potential Clinical Drug Candidate for Drug-Resistant Tuberculosis

Molecules. 2020 Dec 2;25(23):5685. doi: 10.3390/molecules25235685.

Abstract

According to WHO report, globally about 10 million active tuberculosis cases, resulting in about 1.6 million deaths, further aggravated by drug-resistant tuberculosis and/or comorbidities with HIV and diabetes are present. Incomplete therapeutic regimen, meager dosing, and the capability of the latent and/or active state tubercular bacilli to abide and do survive against contemporary first-line and second line antitubercular drugs escalate the prevalence of drug-resistant tuberculosis. As a better understanding of tuberculosis, microanatomy has discovered an extended range of new promising antitubercular targets and diagnostic biomarkers. However, there are still no new approved antitubercular drugs of routine therapy for several decades, except for bedaquiline, delamanid, and pretomanid approved tentatively. Despite this, innovative methods are also urgently needed to find potential new antitubercular drug candidates, which potentially decimate both latent state and active state mycobacterium tuberculosis. To explore and identify the most potential antitubercular drug candidate among various reported compounds, we focused to highlight the promising lead derivatives of isoniazid, coumarin, griselimycin, and the antimicrobial peptides. The aim of the present review is to fascinate significant lead compounds in the development of potential clinical drug candidates that might be more precise and effective against drug-resistant tuberculosis, the world research looking for a long time.

Keywords: antimicrobial peptides; coumarin derivatives; drug-resistant tuberculosis; isoniazid derivatives.

Publication types

  • Review

MeSH terms

  • Animals
  • Antitubercular Agents / pharmacology*
  • Coumarins / chemistry
  • Drug Design*
  • Humans
  • Isoniazid / chemistry
  • Mycobacterium tuberculosis / drug effects*
  • Peptides, Cyclic / chemistry
  • Pharmaceutical Preparations / administration & dosage*
  • Pharmaceutical Preparations / chemistry*
  • Pore Forming Cytotoxic Proteins / chemistry
  • Tuberculosis, Multidrug-Resistant / drug therapy*
  • Tuberculosis, Multidrug-Resistant / microbiology

Substances

  • Antitubercular Agents
  • Coumarins
  • Peptides, Cyclic
  • Pharmaceutical Preparations
  • Pore Forming Cytotoxic Proteins
  • griselimycin
  • coumarin
  • Isoniazid