Advances in Drug Discovery of New Antitubercular Multidrug-Resistant Compounds.

Guilherme Fernandes,Chung Man Chin,Jean Dos Santos

doi:10.3390/ph10020051

Guilherme Fernandes, Chung Man Chin + Show 1 more

Open Access

https://doi.org/10.3390/ph10020051

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Journal: Pharmaceuticals	Publication Date: Jun 1, 2017
Citations: 36	License type: CC BY 4.0

Affiliation: Universidade Estadual Paulista (Unesp)

Abstract

Tuberculosis (TB), a disease caused mainly by the Mycobacterium tuberculosis (Mtb), is according to the World Health Organization (WHO) the infectious disease responsible for the highest number of deaths worldwide. The increased number of multidrug-resistant (MDR-TB) and extensively drug-resistant (XDR-TB) strains, and the ineffectiveness of the current treatment against latent tuberculosis are challenges to be overcome in the coming years. The scenario of drug discovery becomes alarming when it is considered that the number of new drugs does not increase proportionally to the emergence of drug resistance. In this review, we will demonstrate the current advances in antitubercular drug discovery, focusing on the research of compounds with potent antituberculosis activity against MDR-TB strains. Herein, active compounds against MDR-TB with minimum inhibitory concentrations (MICs) less than 11 µM and low toxicity published in the last 4 years in the databases PubMed, Web of Science and Scopus will be presented and discussed.

Highlights

According to the World Health Organization (WHO), tuberculosis (TB) is the infectious disease responsible for the highest number of deaths worldwide, surpassing even the number of deaths caused by the human immunodeficiency virus (HIV)
Mahajan and Dhawale reported the synthesis of a series of thiadiazoles derivatives as promising candidates for resistant tuberculosis treatment
The in vivo efficacy of this compound was assessed in a mouse infection model and it was able to reduce the bacterial burden on a logarithmic scale of 2.12 log10 CFU at 100 mg kg−1 dosage level in the lungs after 4 weeks of treatment protecting the mice from death

Summary

Introduction

According to the World Health Organization (WHO), tuberculosis (TB) is the infectious disease responsible for the highest number of deaths worldwide, surpassing even the number of deaths caused by the human immunodeficiency virus (HIV). Regarding MDR-TB, the drug pipeline presents six compounds in phase 2 and 3 trials. PDhaermspacietuetictahlse20r1e7c,e10n,t51advances, strains resistant to these new molecules have already been2roefp17orted [10,11,12] reinforcing the urgent need to develop novel drugs for tuberculosis treatment. All MIC values against MDR-TB strains presented

Results

Conclusion