INTRODUCTION:
Heterocyclic compounds are cyclic compounds with at least one atom like N, O, S, P, Si, B and Se other than carbon in the ring and the ring itself is called a heterocycle. Heterocyclic compounds are highly attractive compounds in the research and development of bioactive compounds for pharmaceutical industry1. In1887 thiazole ring was synthesized by Rudolf Hantzch. Heterocycles are divided into aromatic and saturated heterocycles and it can be further classified as four-, five-, six-, and seven-membered heterocycles.
Heterocycles carry out several essential processes inside our body, for example, nerve impulse transmission, provision of energy2, metabolism, sight, transfer of hereditary information, etc., as observed by heterocyclic compounds, such as enzymes, vitamins, coenzymes, DNA, RNA, ATP and serotonin3. Due to their wide range of actions, thiazoles are an essential five-membered hetrocyclic ring. Many hetrocyclic compounds with a wide range of actions, such as antibiotics, antimicrobials4, antidiabetic, anticancer5, anti-inflammatory, antimycobacterial6, antiprotozoal and diuretics effects7.
Thiazole is a five-membered heterocyclic molecule with one sulphur and one nitrogen atom in the ring, also known as 1,3-azole. Isothiazoles are nitrogen and sulphur-containing chemicals that are formed when 1,2-azoles8 are in isomeric state.
Chemistry of Thiazole:
In hetrocyclic thiazoles, the electron-donating group (-S) and the electron-accepting group (C=N) are both present. Thaizole is a transparent pale yellow liquid with a boiling point of 116-1180C that is soluble in alcohol and ether but only weakly soluble in water.
Electrophilic substitution occurs at the C4-position, according to the computed -electorns density9. Nuclear substitution occurred at the C2 location.
Calculated π-electron density of thiazole
The acidity given by the presence of three H-atoms decreases in the order H2 ≥≥ H5≥ H4.
Literature Review:
Antibiotics:
Thaizole, as a fused ring, is an important component of the natural penicillin medicine nucleus, also known as an antibiotic. Antibacterials that target a broad range of gram-positive bacteria. Alexander Fleming discovered the antibiotic penicillin in 1928. Penicillin's molecular structure as a basis for a fussed ring thiazole.
Many cephalosporin derivatives have thiazole derivatives in their chemical structure (e.g. Cefdinir). Cefdinir is a semisynthetic third-generation cephalosporin with action against Gram (+)ve and Gram(-)ve bacteria10. As illustrated in Figure, novel 2-aminothiazole derivatives as 4th generation cephalosporins were released in 2007. Gram negative bacteria were shown to be more active than Gram positive bacteria11.
Antimicrobial Activity:
Thiazole and 2-aminothiazole derivatives show good antimicrobial activity12. The Sulfthiazole is a short acting sulfa drug as an antimicrobial drug shown in figure:
Various thiazole compounds have been utilised as antiviral agents against a variety of viruses, including SARS, HRV, HCV, TMV, YFB, RSV, and influenza. Ritonavir is an antiretroviral drug used to treat HIV/AIDS.
The most active thiazole compounds showed equivalent antifungal activity to Ketoconazole and fluconazole against all Candida strains, according to antifungal screening results13. Several investigations are being conducted with the goal of synthesising thiazole derivatives with high antifungal activity.These derivatives with polyoxygenated phenyl module have exhibited encouraging antifungal activity14. The example for this type of activity is Abafungia.
Antidiabetic Activity:
Various compounds containing heterocyclic rings with nitrogen and sulfur have been reported for their potential biological activity15. Babar et al.(2017) synthesized a series of new ethyl 2-[aryl(thiazol-2-yl) amino] acetates from N-arylthiazole-2-amines and screened its α-glucosidase and β-glucosidase inhibitory activities. Compound (1) and compound (2) displayed excellent inhibitory action towards α-glucosidase, compound (3) and compound (4) displayed the highest inhibitory action towards β-glucosidase.
Compounds (1) and (3) were found to have inhibition potential towards β-glucosidase and molecular docking study also revealed that compounds exhibited antidiabetic potential16 by displaying strong binding interaction with β-glucosidase (PDB: 1CBG).
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Structure No. |
R1 |
R2 |
R3 |
|
1 |
Cl |
Cl |
H |
|
2 |
Br |
H |
H |
|
3 |
F |
H |
|
|
4 |
Br |
H |
|
Sravanthi et al. (2017) synthesized a series of 2-(5-(1H-indol-3-yl)-3-phenyl1Hpyrazol-1-yl)-4-(4-substituted phenyl) thiazole derivatives and screened its α-glucosidase and α-amylase inhibitory activity. Compound 2-(5-(1H-Indol-3-yl)-3-phenyl-1H-pyrazol-1-yl)-4(4-bromo phenyl) thiazole (5) displayed excellent inhibitory potential and compounds such as (6) and (7) having fluoro and hydroxyl substituent on phenyl ring of the thiazole moiety also showed remarkable inhibitory activity.
Compounds (5) showed excellent in vitro antihyperglycemic activity against α-glucosidase and α-amylase and molecular docking study also revealed that compound showed strong binding interaction with α-amylase and αglucosidase (PDB:1NHZ)17.
|
Structure No. |
R1 |
R2 |
|
5 |
Br |
H |
|
6 |
F |
H |
|
7 |
H |
H |
Mao et al. (2012) reported a novel series of thiazole containing benzamide derivatives and investigated for glucokinase (GK) activator ability. Compound 8 was found to be most promising antidiabetic agent . The high activity of thiazole derivative 8 was attributed to presence of cyclic secondary amine, which may involve in hydrogen bonding with target site18.
Anticancer Activity:
Thiazole compounds have been found to have cytotoxic potential against a variety of cell lines, and one of the oral marketed drugs is Dasatinib (Sprycel), which inhibits a number of tyrosine kinases including Bcr-Abl and the Src kinase family19. Dabrafenib is an anticancer drug that is used to treat adult cancer patients.
Bleomycin is an antibiotic anticancer agent that can be used to treat a variety of malignancies.
Anti-Inflammatory Activity:
Nonsteroidal anti-inflammatory drugs (NSAIDs), like aceclofenac, ibuprofen and ketoprofen are used to cure of inflammatory disorders20. Thiazole derivatives containing drugs which are used to treat inflammatory disorders are like fanetizole, meloxicam and Sudoxicam21.
Compounds (1) and (2) which displayed anti-inflammatory activity in a mouse model of albumin-induced allergy/asthma by reducing the lung inflammation. These Compounds exhibited the potent inhibition of T-cell activation which developed immunosuppressive agent to cure inflammation and autoimmune disorder also diminished calcium mobilization, PLCγ1 tyrosine phosphorylation and IL-2 secretion.
Compounds such as (1) (having p-OCH3) and (2) (with p-Cl) and (3) (with OCH3 group) and(4) (with p-Cl) displayed most potent anti-inflammatory activity. These Compounds was found to have inhibition potential against PGF2alpha (COX pathway) and LTB4 (LOX pathway) and showed excellent antiinflammatory activity22.
|
Structure No. |
R1 |
R2 |
|
3 |
OCH3 |
|
|
4 |
Cl |
|
|
5 |
OCH3 |
|
|
6 |
Cl |
|
Anti-Mycobacterial Activity:
Thizole derivatives having target specificity and potent inhibitor of MTB are of particular interest. 2-Aminothiazoles scaffold is basically similar to thiolactomycin, which is challenging antibiotic and inhibits KasA (β- ketoacyl-ACP synthase) in mtFabH fatty acid synthesis and therefore inhibiting cell wall synthesis leading to cell death. Nitazoxanide, and its active metabolite are well known for their inhibitory activity against replicative and nonreplicative Mtb.
2-aminothiazoles and tested them for inhibitory action against M. tuberculosis strains that were actively nonreplicating, replicating, and resistant. N-phenyl-5-(2-(p-tolylamino) thiazol-4-yl) isoxazole-3-carboxamide (MIC 0.1250.25g/ml) and N-(pyridin-2-yl)5-(2-(p-tolylamino) thiazol-4-yl) isoxazole-3-carboxamide (MIC 0.060.125g/ml) were shown to have excellent inhibitory activity23.
Diuretic Effects:
Etozolin, a novel Qzolinone prodrug, and the (L) isomer The active chemical form is etozolin, while the inactive (D)Isomer is ozolinone, a tautomeric version of thizolidine24. The enzymetic hydrolysis metabolism viia phase(1) metabolism as shown in figure:
SYNTHESIS OF THIAZOLE DERIVATIVES:
A) Gabriel synthesis-The 2,5-disubstituted thiazole were synthesized by the reaction of an acylamino-ketone with phosphorus pentasulfide25.
B) The Hantzsch thiazole synthesis:
Thiazole derivative was synthesized by the reaction of thiomide and haloketone in the presence of methanol or ethanol.
C) The Cook-Heilbronthiazole synthesis- The 5-amino-2-mercaptothiazole were synthesized from the reaction of α-amino nitriles with carbon disulphide26.
D) Synthesis of 2-Aminothiazole from the reaction of N-(2-bromoprop-2-enyl) thioamides via intramolecular nucleophilic substitution reaction27.
E) 2-Aminothiazole were synthesized from the reaction of bromoacetophenone with thiourea28.
F) 2-Aminothiazole were synthesized from the reaction of propargyl bromide with thiourea29.
CONCLUSION:
This review article wraps several literatures of the thiazole derivatives in the field of medicinal chemistry. The thiazole and its derivatives show a variety of pharmacological activities which plays important role such as antibiotics, antimicrobials, antidiabetic, anticancer, anti-inflammatory, antimycobacterial, antiprotozoal and diuretics effects. The different ways of synthesis to thiazole and its derivatives are compacted in this article.
ACKNOWLEDGMENTS:
All authors are greatfull to our director, and management committee of Amar Saheed Baba Ajit Singh Jujhar Singh Memorial College of Pharmacy BELA, Ropar Punjab, India for their support.
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Received on 27.04.2022 Modified on 03.12.2022
Accepted on 13.06.2023 © RJPT All right reserved
Research J. Pharm. and Tech 2023; 16(10):4981-4986.
DOI: 10.52711/0974-360X.2023.00806