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Repositioning of Isatin hybrids as novel anti-tubercular agents overcoming pre-existing antibiotics resistance

Abstract

The widespread deaths of tuberculosis from many decades demands an urgent need for the development of novel anti-tubercular scaffolds that are more potent and highly selective with lower cytotoxicity. Isatin hybrids are endowed with an extensive range of biological activities. Hybridization of isatin with various heterocyclic moieties such as benzofuran, coumarin, tetrahydropyrimidine, quinoline, and well-known drugs like Moxifloxacin, Ciprofloxacin, and so on may provide promising anti-tubercular candidates. This review focuses on the recent developments of isatin-based hybrids possessing potential anti-tubercular activity along with the novel drugs under various phases of clinical trials for the treatment of tuberculosis. The structure-activity relationships are also discussed to provide insights into the potential anti-tubercular candidates.

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Abbreviations

MTB:

Mycobacterium tuberculosis

M. Tb.:

Mycobacterium tuberculosis

TB:

Tuberculosis

LTBI:

Latent Tuberculosis Infection

HIV:

Human immunodeficiency virus

WHO:

World Health Organization

MDR-TB:

Multidrug-Resistant Tuberculosis

RR-TB:

Rifampicin-Resistant Tuberculosis

MTB DR:

Mycobacterium tuberculosis Drug Resistant

XDR-TB:

Extensively Drug Resistant Tuberculosis

TDR-TB:

Totally Drug Resistant Tuberculosis

UN:

United States

TST:

Tuberculin Skin Test

IGRA:

Interferon-Gamma Release Assay

QFT:

QuantiFERON-TB

PET-CT:

Positron Emission Tomography and Computed Tomography

DST:

Drug Susceptibility Testing

LAMP:

Loop-Mediated Isothermal Amplification

WGS:

Whole Genome Sequencing

LPA:

Line Probe Assay

DOT:

Directly Observed Therapy

ART:

Antiretroviral Therapy

INH:

Isoniazid

RIF:

Rifampicin

CPFX:

Ciprofloxacin

MXF:

Moxifloxacin

GTFX:

Gatifloxacin

PPI:

Protein-protein interactions

MIC:

Minimum Inhibitory Concentration

CC:

Cytotoxic Concentration

IC50 :

Half maximal inhibitory concentration

SI:

Selectivity Index

RI:

Resistance Index

DR-TB:

Drug resistant tuberculosis

SAR:

Structure-activity relationship

NAD:

Nicotinamide adenine dinucleotide

BACTEC MGIT:

Becton Dickinson Mycobacteria Growth Indicator Tube

RNA:

Ribonucleic acid

DNA:

Deoxyribonucleic acid

ADMET:

Adsorption, Distribution, Metabolism, Excretion, and Toxicity

MOE:

Molecular Operating Environment

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Acknowledgements

Authors acknowledge Department of Chemistry, University of Delhi, India. P.T is thankful to Council for Scientific and Industrial Research, New Delhi, India for the grant of Junior Research Fellowship.

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Kumar, R., Takkar, P. Repositioning of Isatin hybrids as novel anti-tubercular agents overcoming pre-existing antibiotics resistance. Med Chem Res 30, 847–876 (2021). https://doi.org/10.1007/s00044-021-02699-5

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