Drug development against tuberculosis: Past, present and future

Mahesh S Vasava; Manoj N Bhoi; Sanjay K Rathwa; Mayuri A Borad; Sneha G Nair; Hitesh D Patel

doi:10.1016/j.ijtb.2017.03.002

Drug development against tuberculosis: Past, present and future

Indian J Tuberc. 2017 Oct;64(4):252-275. doi: 10.1016/j.ijtb.2017.03.002. Epub 2017 Apr 14.

Authors

Mahesh S Vasava¹, Manoj N Bhoi², Sanjay K Rathwa², Mayuri A Borad², Sneha G Nair², Hitesh D Patel³

Affiliations

¹ Department of Chemistry, School of Sciences, Gujarat University, Ahmedabad, India. Electronic address: maheshvasava@gujaratuniversity.ac.in.
² Department of Chemistry, School of Sciences, Gujarat University, Ahmedabad, India.
³ Department of Chemistry, School of Sciences, Gujarat University, Ahmedabad, India. Electronic address: drhiteshpatel1@gmail.com.

PMID: 28941848
DOI: 10.1016/j.ijtb.2017.03.002

Abstract

Infection of Mycobacterium tuberculosis (MTB) was observed as early as 5000 years ago with evidence, which is a primeval enemy of the humanoid race. MTB is the pathogen which is responsible for causing the infectious disease tuberculosis; it remains a major cause of morbidity and mortality in poor low-income countries as well as in developing countries because of non-availability of reliable laboratory facilities. The current treatment for drug-resistant tuberculosis (TB) is lengthy, complex, and connected with severe harmful side effects and poor outcomes. The present cure against tuberculosis has substantial restrictions, in terms of their efficiency, side-effect outline, and complication of handling. Furthermore, the emergence of multi-drug resistant tuberculosis (MDR-TB) outbreaks during the 1990s and additionally in recent times the vast deadly strains of extensively drug-resistant tuberculosis (XDR-TB) and totally drug resistance tuberculosis (TDR-TB) is hampering efforts to control and manage tuberculosis (TB). As a result, novel methodologies for the treatment of multi-drug-resistant and extensive drug-resistant tuberculosis (TB) are severely desired. A number of new potential anti-tuberculosis drug candidates with novel modes of action have been entered in clinical trials in recent years. These agents are most likely to be effective against resistant strains. The treatment landscape is beginning to shift, with the recent approvals by Food and Drug Administration to the new TB drugs bedaquiline and delamanid. Also, the pipeline of potential new treatments has been fulfilled with several compounds in clinical trials or preclinical development with promising activities against sensitive and resistant MTB bacteria. An additional new chemical entity is also under development. The already existing drugs with their suggested mode of treatment as well as new probable anti-tuberculosis drug moieties which are at present in the pipeline has been summarized in this review.

Keywords: Anti-TB agents; Antimicrobials; Drug development; Drug resistance; Tuberculosis.

Publication types

Review

MeSH terms

Antitubercular Agents*
Drug Development*
Extensively Drug-Resistant Tuberculosis / drug therapy
Tuberculosis / drug therapy*

Substances

Antitubercular Agents