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DOI: 10.1055/a-2637-7462
Thiazole-Scaffold-Based Anti-tubercular Agents: A Review on Synthesis and Structural Modifications
Authors
Author (AK) is thankful to University of Petroleum and Energy Studies (UPES), Dehradun for providing institutional research fellowship grant to perform this work. Authors (AK, UD, and KKR) are thankful to UPES, Dehradun for providing the necessary infrastructural support.

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 tuberculosisPublication History
Received: 09 April 2025
Accepted after revision: 16 June 2025
Accepted Manuscript online:
17 June 2025
Article published online:
29 July 2025
© 2025. Thieme. All rights reserved
Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
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