1. INTRODUCTION :

1.1 Chemistry of 2-aminothiazole:

Thiazole, also known as 1,3-thiazole, is a clear-to pale-yellow liquid that burns easily. It has the chemical formula C₃H₃NS and smells like pyridine.¹ It is a five-membered ring with three carbons at its vertices and nitrogen and sulfur as heteroatoms. The naming Figure. 1. for Chemical structures of thiazole and 2-aminothiazole is displayed below.²

Figure. 1. Chemical structures of thiazole and 2-aminothiazole

According to Huckel's rule, the heterocyclic ring of thiazole has a delocalization of five π electrons from the lone pair electrons, which is the sulphur atom.³ The resonance forms of thiazole are shown in Figure. 2. Thiazoles are more aromatic than their analogues, such as oxazole, because of their stronger pi-electron delocalization.⁴

Figure. 2. The resonance forms of thiazole.

In pharmaceutical chemistry, the pharmacophore 2-aminothiazole is an intriguing building block that serves as a starting point for the synthesis of numerous heterocyclic compounds with various kinds of biological activity, including antimicrobial, antifungal, anti-tuberculosis, anti-cancer, and anti-inflammatory properties.⁵ For instance, the anti-HIV medication ritonavir has a 5-substituted oxymethyl thiazole moiety, and imidacloprid, an isostere of the significant pesticide, contains 2-chloro-5-substituted methylthiazole in its structure.⁶ Many thiazole compounds were created to target particular pathways and are known to have significant antitumor or cytotoxic effects. Examples of these thiazole-containing drugs that have been used in cancer treatment and clinical trials include dasatinib and dabrafenib, which have tyrosine kinase inhibitory action.⁷ The drug with a 2-aminothiazole nucleus that has been approved to treat peptic ulcers and gastroesophageal reflux is famotidine. Other examples are the NSAID meloxicam and the pharmaceutical abafungin, which is used to treat dermatomycoses. Some examples of thiazole containing drugs sold in the market is displayed in Figure. 3.

Figure. 3. Some examples of thiazole containing drugs sold in the market.

1.2 Chemistry of Schiff base complexes:

Imine was first prepared by Hugo Schiff in the 19th century.⁸ An aldehyde or ketone is combined with a primary amine to create a Schiff base, which is accomplished by substituting an imine group with an aldehyde or ketone carbonyl group, as shown in Scheme 1.

Scheme 1: General synthesis reaction of Schiff base

Because of the compounds' outstanding antibacterial, antifungal, and anticancer activity, the azomethine C=N link is crucial to their effectiveness.⁹ Schiff bases are used extensively in the pharmaceutical sector. Schiff bases also serve as significant metal ligands by interacting with other donor groups and the imine nitrogen atom. This is because Schiff bases can attach to metals at various locations to create complexes such as Cu (II), Ni (II), Co (II), or Zn (II)¹⁰ Coordination between the metal ion and donor centres of imines and other molecules. Since the form, size, distribution, redox potential, and charge density variations of these Schiff bases impact the biological activity of the ligand, the metal complexes that are produced from them have garnered particular interest in the medical and pharmaceutical fields.¹¹ As a consequence, numerous studies have been conducted using established Schiff base complexes containing aminothiazoles to evaluate the antibacterial and antifungal properties of these compounds.¹²

1.3 Advantages of microwave-assisted synthesis:

Efficient, less expensive, and clean procedures have gained more attention in recent years as they have fostered environmental awareness in chemical research and industry. In coordination chemistry, there is an urgent need to develop a new, straightforward procedure that is both affordable and environmentally benign. Recent technological advancements have improved the efficiency of heating reactions using microwave energy.¹³ Chemical changes that require hours or even days to complete their organic reaction can now be completed in a matter of minutes. Because polar molecules selectively absorb microwaves, microwave irradiation facilitates the synthesis of a wide range of organic and inorganic compounds, resulting in quicker chemical procedures.¹⁴ Green chemistry includes the microwave-assisted method. The application of microwave-assisted synthesis in coordination, inorganic, and organometallic chemistry continues to develop at a continuous space.¹⁵ Reactions that get microwave-irradiated in solvent-free or less solvent conditions are outstanding, exhibit lower pollution, are inexpensive, provide good yields, and are simple to handle and process. The salient features of the microwave method are faster reaction times, easier reaction conditions, and enhanced yields, as shown in Figure. 4.

Figure. 4. The salient features of the microwave assisted synthesis.

2. Microwave Assisted Synthesis of Organometallic-2-Aminothiazole Derivatives and their Biological Activity:

The organometallic chemistry of thiazole derivatives has emerged as a pivotal area bridging heterocyclic ligand design with transition metal coordination, offering promising applications across catalysis, materials science, and medicinal chemistry. Thiazole scaffolds, containing both nitrogen and sulfur donor atoms, readily form stable chelates with transition metals such as Cu (II), Ni (II), Pd (II), and Fe (II), significantly altering the electronic and steric properties of resulting complexes.¹⁶ These structural features not only enable enhanced catalytic performance but also impart notable bioactivity.

Microwave-assisted synthesis has emerged as a powerful green chemistry approach, offering significant advantages including reduced reaction times, higher product yields, and improved purity.¹⁷ The combination of microwave-assisted synthesis with organometallic coordination chemistry represents a versatile strategy for the rapid development of functional thiazole-based compounds, paving the way for new applications in therapeutic design and advanced materials. Copper and zinc metal complexes of the 2-aminothiazole Schiff base 4-aminoantipyrine were discovered, as shown in Scheme 2. They show substantial biological activity.¹⁸ Using tetracycline as the standard of reference, the antibacterial properties of the ligand Schiff base and its metal complexes were evaluated against the following bacteria: Pseudomonas aeruginosa, Bacillus subtilis, Escherichia coli, and Staphylococcus aureus. When compared to the free ligand, the metal complexes exhibit higher lipophilicity, which improves cell membrane penetration and increases antibacterial activity.¹⁹ Alternatively, the combined activity of the metal and ligand may be the reason for the high activity. As demonstrated, in the in-silico DNA-metal complex combination, all complexes interacted with DNA. These complexes had greater action than the ligand in antimicrobial studies against Staphylococcus aureus, Escherichia coli, Bacillus subtilis, and Pseudomonas aeruginosa.²⁰

Scheme 2: Copper and zinc complexes with the 2-aminothiazole Schiff base of 4-aminoantipyrine.

Using the microwave-assisted synthesis of a novel Schiff base of salicylalidene-4-iminoantipyrine and 2-aminothiazole, their transition metal complexes were prepared, as shown in Scheme 3. The full structural characteristics of the produced compounds were followed by antibacterial research on a few bacteria and fungi, as well as DNA interaction studies.²¹

Scheme 3. Schiff base of salicylalidene-4-iminoantipyrine and 2-aminothiazole and transition metal complexes

Intercalation occurs between the complex and DNA binding, per research on the interaction of the copper-compound complex with DNA. High growth inhibition for the chelates was the outcome of studies on breast cancer cell lines examining the anticancer effects of Schiff bases and their metal complexes.²² Additionally, utilizing the well diffusion method, an antibacterial research of Schiff bases and their metal complexes was conducted on G- (E. coli, Klebsiella pneumoniae, and Salmonella typhi), G+ (Staphylococcus aureus and Bacillus subtilis), and fungal species. Because of their greater lipid solubility, the Cu- and VO-ligand complexes are thought to have a greater inhibitory impact than the Schiff base. The molecule works by creating a hydrogen connection between the azomethine atom and the active centre of the cell, which prevents normal cell growth.²³

Scheme 4 shows the synthesis of 2-hydroxybenzylidene-4-(4-substitutedphenyl)-2-amino-thiazole Schiff bases and their platinum complexes using a microwave oven, where platinum ions bond to both the hydroxyl group of an aromatic ring and the imine group of Schiff bases in a square planar complex.²⁴ Their biological activities were then investigated.

Scheme 4: Synthesis of 2-Hydroxybenzylidene-4-(4-Substituted Phenyl)-2-amino-thiazole Schiff base with platinum complex.

The platinum complexes are more active, according to an antioxidant analysis of the Schiff bases and their complexes. Since it is well known that the anti-oxidation process entails the transfer of protons or electrons from the antioxidant compound to the free radical, resulting in a stable neutral compound that terminates the free radical chain reaction, platinum metal increases the electron stability of radicals.²⁵ Schiff bases' IC₅₀ is larger (more inhibitory effect) than that of their corresponding Pt (II) complexes, according to cytotoxicity measurements conducted on the human breast cancer cell line (MCF-7) using Schiff bases and their platinum complexes.²⁶ Microwave assisted synthesis of a 10 mmol ethanolic solution (1.52 g) of 2-hydroxy-3-methoxybenzaldehyde was added to a 10 mmol ethanolic solution of 2-methoxy-6-((thiazol-2-ylimino)methyl) phenol to produce the ligand shown in Scheme 5. The mixture was refluxed for 1-5 min and the reaction's progress was tracked using the TLC method. The answer was considered complete when the hue shifted, and a single TLC spot appeared. The solvent was evaporated using a rotating vacuum evaporator to recover the product.²⁷ The product was further purified by washing it in a hot ethanol/ether (1:1) solution. The previously specified method was used to synthesize the metal complexes, with a metal-to-ligand ratio of 1:2. A magnetically refluxed (100mmol) ethanolic solution of the ligand was mixed with a 50mmol solution of the appropriate metal salt in ethanol, and the mixture was refluxed for 1-10 min, resulting in product precipitation. The filtered product was then rinsed in hot ethanol to further purify it.²⁸

Scheme 5: Synthesis of Thiazole-Based Ligands and Their Metal Complexes.

Ferrocenyl–thiazole conjugates, shown in Scheme 6. were synthesized via condensation of diacetylferrocene with 2-amino-5-methylthiazole, yield metal complexes with Pb(II), Co(II), Ni(II), Cu(II), and Zn(II) that exhibit potent anticancer activity against MCF-7 breast cancer cells, with efficacy comparable to cisplatin through ROS-mediated mechanisms.²⁹ Additionally, a range of Fe(III), Pd(II), and Cu(II) thiazole-based complexes have been characterized via DFT, DNA-binding studies, and cytotoxicity assays, demonstrating potential as multifunctional therapeutic agents.³⁰ Beyond biomedical relevance, thiazole-based organometallic systems are also being harnessed in the development of optoelectronic devices, molecular switches, and chemical sensors, leveraging π–π stacking and chalcogen bonding to fine-tune material properties.³¹ These advances affirm the versatility of thiazole ligands in driving innovation at the interface of coordination chemistry and functional materials science.

Scheme 6: Synthesis of Ferrocenyl–Thiazole conjugates and Their Metal Complexes.

CONCLUSION:

Thiazole moieties have taken centre stage in contemporary organic and medicinal chemistry due to their wide range of pharmacological and therapeutic properties, which include antibacterial, anticancer, and antioxidant effects. The thiazole ring found in numerous medications, including dabrafenib, dasatinib, famotidine, abafungin, and meloxicam, encourages chemists to create novel thiazole scaffolds. Due to their versatile coordination ability toward a variety of transition metal ions, multidonor thiazole ligands with both nitrogen and sulphur atoms have attracted a lot of interest, especially in the synthesis and applications of bioactive coordination compounds. In this present review, 2-aminothiazole scaffolds containing Schiff bases are used as powerful binding agents in coordination chemistry to prepare an active complex that exhibits a broad spectrum of pharmacological activities. So designing new and more effective therapeutics requires an understanding of the organometallic thiazole derivatives. Researchers can optimize the compound's characteristics for a particular biological target by methodically altering the organometallic thiazole ring. The recent synthesis of 2-aminothiazole Schiff bases and the examination of their antibacterial and anticancer properties as Schiff bases or metal complexes are the main topics of this review. To create novel complexes for various biological targets, this review will assist in the construction of new thiazole Schiff-based compounds and their chelation as ligands with transition metals.

CONFLICT OF INTEREST:

The authors have no conflicts of interest regarding this investigation.

ACKNOWLEDGMENTS:

I am deeply grateful to Dr. Sevak B Gurubaxani, for their invaluable guidance and feedback on this paper. Their insightful comments and suggestions significantly contributed to the improvement of this work.

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Received on 27.07.2025 Revised on 16.08.2025

Accepted on 01.09.2025 Published on 30.09.2025

Available online from October 07, 2025

Asian J. Research Chem.2025; 18(5):357-362.

DOI: 10.52711/0974-4150.2025.00055

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