Abstract
Tuberculosis (TB), caused by Mycobacterium tuberculosis, remains a major global health challenge due to the rise of multidrug-resistant (MDR)
and extensively drug-resistant (XDR) strains. The urgent need for novel anti-tubercular
agents has driven extensive research in heterocyclic scaffolds, with thiazole-based
compounds emerging as promising candidates. Thiazole-based compounds exhibit potent
anti-tubercular activity by targeting key bacterial enzymes, disrupting cell wall
synthesis, and interfering with essential metabolic pathways. Thiazole ring compounds
show significant biological activity due to their versatile chemical nucleophilic
and electrophilic reactivity. This review provides a comprehensive analysis of the
conventional and modern synthetic approaches for thiazole-scaffold-based anti-tubercular
agents. Additionally, it explores structural and functional group modifications on
the thiazole core and their impact on anti-tubercular activity. Recent advancements
in molecular modeling, hybrid molecule design, and medicinal chemistry strategies
for optimizing thiazole derivatives are also discussed. The insights presented in
this review highlight the potential of thiazole scaffolds in TB drug discovery and
underscore the need for further medicinal chemistry, preclinical and clinical investigations
to develop effective and safer TB therapeutics.
1 Introduction
1.1 Chemical Reactivity of the Thiazole Ring
1.2 Different Conventional Methods Used for the Synthesis of Substituted Thiazoles
as Anti-tubercular Agents
1.2.1 Hantzsch Thiazole Synthesis
1.2.2 Gabriel Synthesis
1.2.3 Cook–Heilbron Synthesis
1.2.4 Other Reported Methods
2 Small Molecule Inhibitors (SMIs) as Anti-tubercular Agents
2.1 Phenyl-thiazole Derivatives
2.2 Imidazo[2,1-b]thiazoles
2.3 Carbazolo-thiazole Derivatives
2.4 Thiazole-chalcone Derivatives
2.5 Bis-thiazole Derivatives
2.6 2,4,5-Trisubstituted Thiazole Derivatives
2.7 Hydrazine-thiazole Derivatives
2.8 Thiazolidinone Derivatives
2.9 Carboxamide-thiazole Derivatives
2.10 Benzothiazole Derivatives
2.11 Amino-thiazole Derivatives
2.12 Thiazole-thiadiazole Derivatives
2.13 Thiazole-coumarin Derivatives
2.14 Pyrazolyl-thiazole Derivatives
2.15 Sulfonyl-thiazole Derivatives
2.16 Summary of Anti-tubercular Targets in Section 2
3 Molecular Modeling Analysis
4 Challenges of Mutations and Future Perspectives
5 Recent Advances in Clinical Trials for Anti-tubercular Drug Development
6 Conclusion
Key words
tuberculosis - drug resistance - thiazole scaffold - medicinal chemistry -
Mycobacterium tuberculosis
