Unveiling the Therapeutic Potential of Compounds Carrying Mono- and Bis-Thiazole Nuclei with Distinct Heterocyclic Analogues for Addressing Cancer Challenges.

Abstract

Background: The thiazole nucleus serves as a bioactive synthetic scaffold in drug design and discovery due to its diverse pharmacological activities. It was discovered that many types of thiazole derivatives, including those with one, two, or three substitutions, five- or six-membered heterocycles, fused rings, and thiazole-derived Schiff bases, hydrazinyl derivatives, amides, chalcones, and bis-thiazoles, can fight cancer. Thus, the structural diversity of thiazole nuclei makes it one of the significant areas of research in the pharmaceutical field.

Objective: We would like to elaborate on the recent literature available on the antiproliferative property of molecules bearing 1,3-thiazole nuclei.

Methods: This review summarises the anticancer potency of thiazole derivatives collected from recently available scientific literature. We extracted the information from online databases like PubMed, Scopus, and Web of Science using relevant keywords from 2016 to the present. We discuss the current state of thiazole derivatives and highlight the most promising compounds. We also describe how they work and what their half-maximum inhibitory concentration (IC50) is.

Results: Based on our extensive literature review, we found that thiazole derivatives exhibit anticancer activity through their ability to induce apoptosis in cancer cells, mitochondrial membrane disruption by blocking signalling pathways such as Akt, NFkB, PI3K, and Src/Abl, and inhibition of proteins responsible for cell growth. Moreover, thiazole-protein interactions essential for cancer inhibition are predominantly regulated by hydrogen bonding, supported by the sulphur and nitrogen atoms in the thiazole molecule, which effectively interacts with the amino acids serine, tyrosine, and glutamine. π-π stacking and π-cation interactions involving aromatic amino acids such as tryptophan, tyrosine, and phenylalanine, along with hydrophobic effects and van der Waals forces, play a crucial role in thiazole-protein interactions. These interactions dictate binding affinity and efficacy, measured through thermodynamic characteristics such as Binding Constant (Kb), Dissociation Constant (Kd), and Gibbs free energy (ΔG). Comprehending these features is essential for the development of effective thiazole-based anticancer pharmaceuticals.

Conclusion: This cumulative information is enough to give new ideas for the rational drug design of thiazole-based derivatives and could be pursued as a promising lead in the future for the management of cancer threats.