logo

International Journal
of Pharmaceutical Sciences and Drug Research

ISSN 0975-248X
CODEN (USA): IJPSPP
DOI PreFix: 10.25004

Volume No.: 1 (2009) Issue No: 3

International Journal of Pharmaceutical Sciences and Drug Research
12009 (2009) ,143Pages

ResearchArticle

Thiazoles: A Valuable Insight into the Recent Advances and Biological Activities


Nadeem Siddiqui*, M. Faiz Arshad, Waquar Ahsan, M. Shamsher Alam

UGC Approved Journal

  • Views 2
  • Citations 46
  • ePub 5
  • PDF 1

1. Abstract


Thiazoles displayed broad range of biological activities and found in many potent biologically active molecules such as Sulfathiazol (antimicrobial drug), Ritonavir (antiretroviral drug), Abafungin (antifungal drug) and Tiazofurin (antineoplastic drug). So far, modifications of the thiazole ring have proven highly effective with improved potency and lesser toxicity. The present review highlights the recently synthesized thiazoles possessing important biological activities.


Introduction


Thiazole is a heterocyclic compound featuring both a nitrogen atom and sulfur atom as part of the aromatic five-membered ring. Thiazole and related compounds are called 1, 3-azoles (nitrogen and one other heteroatom in a five-membered ring). They are isomeric with the 1, 2-azoles, the nitrogen and sulfur compound being called isothiazole. The numbering system is shown below for naming derivatives of thiazole.

Thiazole is aromatic on the basis of delocalization of a lone pair of electrons from the sulfur atom completing the needed 6 π electrons to satisfy Huckel’s rule. The resonance forms are:

*Corresponding author: Prof. Nadeem Siddiqui,

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Jamia Hamdard (Hamdard University), New Delhi 110062, India Tel: +91 11 26059688 Extn 5639.

Email:nadeems_03@yahoo.co.in,

nadeems_03@rediffmail.com

Thiazole is a clear to pale yellow liquid with a boiling point of 116-118oC. Its specific gravity is 1.2 and it is sparingly soluble in water. It is soluble in alcohol and ether. The odor of thiazole is similar to pyridine. It is used as an intermediate to manufacture synthetic drugs, fungicides, and dyes. A thiazole ring is found naturally in the essential vitamin B1 (thiamin).

Thiamin

Thiamin is a water soluble vitamin that helps the body release energy from carbohydrates during metabolism. It also helps in the normal functioning of the nervous system by its role in the synthesis of acetylcholine, a neurotransmitter. Thiamin is found mostly in pasta and breads made from refined flours. It is also found in ready-to-eat cereals and in navy and kidney beans.

1.2. BIOLOGICAL ACTIVITIES

Thiazoles are important class of heterocyclic compounds, found in many potent biologically active molecules such as Sulfathiazol (antimicrobial drug), Ritonavir (antiretroviral drug), Abafungin (antifungal drug) with trade name Abasol cream and Bleomycine and Tiazofurin (antineoplastic drug).

It has been noticed continuously over the years that interesting biological activities [1-2] were associated with thiazole derivatives. Recently the applications of thiazoles were found in drug development for the treatment of allergies [3], hypertension [4], inflammation [5], schizophrenia [6], bacterial [7], HIV infections [8], hypnotics [9] and more recently for the treatment of pain [10], as fibrinogen receptor antagonists with antithrombotic activity [11] and as new inhibitors of bacterial DNA gyrase B. [12] A brief review of thiazoles associated with large number of biological activities is presented below.

1.2.1. Antitumor activity

Ramla et al [13] synthesized a variety of 1-substituted-2-methyl-5-nitrobenzimidazoles and evaluated them for anti-tumor activity. The anti-tumor effect of compound [1] was found to be significant.

Popsavin et al [14] reported a set of 2-(2, 3-anhydrofuranosyl) thiazole-4-carboxamide (2', 3'-anhydro tiazofurin) derivatives and screened them for their anti-tumor activity. The most active compound was found to be [2] against K562 malignant cells, with IC50 vlues ranging from 0.09-0.49 μM.

Gulsory et al [15] presented a series of arylidene hydrazides from [6-(4-bromophenyl) imidazol-3yl] acetic acid hydrazide. The synthesized compounds were evaluated one dose primary cytotoxicity assay. Compound [3] demonstrated the most effective agents on a prostate cancer cell lines.

1.2.2. Anti-inflammatory activity

Kumar et al [16] synthesized a group of 3-[4'(p-chlorophenyl) thiazol-2'-yl]-2-[(substituted azetidinone/thiazolidinone)-aminomethy]-6-bromoquinazolin-4-ones and screened them for anti-inflammatory and analgesic activities. Compound [4] was found to be highly active in both the activities. They found that the presence of thiazolidinone ring have shown much better anti-inflammatory as well as analgesic activity at 50 mg/kg po as compared to their parent compounds. Compound substituted with chloro group at 2nd position of phenyl ring has shown almost equal anti-inflammatory activity to that of the standard drug phenylbutazone at 50 mg/kg.

Holla et al [17] reported different series of arylaminothiazoles, arylidene/5-aryl-2-furfurylidene hydrazinothiazoles and screened them for their antibacterial and anti-inflammatory activities. Two of the newly synthesized compounds [5] and [6] showed anti-inflammatory activity comparable with that of ibuprofen.

Kalkhambkar et al [18] reported triheterocyclic thiazoles containing coumarin and carbostyril (1-aza coumarin). The newly synthesized compounds were tested for their in vitro analgesic and anti-inflammatory activities. Among the tested compounds, [7] and [8] significantly inhibited the acetic acid induced writhing.

Rostom et al [19] reported two groups of structure hybrids comprising basically the antipyrine moiety attached to polysubstituted thiazole or 2, 5-disubstituted-1, 3, 4-thiadiazole counterparts through various linkages. Twelve compounds were evaluated for their anti-inflammatory activity, ulcerogenic effects and acute toxicity. The analgesic activity of the same compounds was also evaluated. Additionally, their in vitro antimicrobial activity was evaluated. Some compounds [9] and [10] displayed remarkable anti-inflammatory and analgesic profiles with a fast onset of action together with a super GI safety profile and safety margin. Additionally, some compounds exhibited broad-spectrum antimicrobial activity.

1.2.3. Antimicrobial activity

Pandeya et al [20] prepared a series of Schiff and Mannich bases derived from isatin derivatives and N-[4-(4'chloropheyl) thiazol-2-yl] thiosemicarbazide. Investigation of antimicrobial activity of compounds was done by agar dilution method against 28 pathogenic bacteria, 8 pathogenic fungi and anti-HIV-1 (IIIB) in MT-4 cells. Among the compounds tested [11] showed the most favorable antimicrobial activity.

Shiradkar et al [21] reported a series of N-{4-[(4-amino-5-sulphanyl-4H-1, 2, 4-triazol-3-yl) methyl]-1, 3-thiazol-2-yl}-2-substituted amide derivatives. The compounds were tested for their preliminary in vitro antibacterial activity against S. aureus, E. coli, P. aeroginosa and S. typhosa and then were screened for antitubercular activity against M. tuberculae H37Rv strain by both micro dilution assay method. Compound [12] and [13] showed best activity. They revealed that the compounds that have shown more than 90% inhibition were obtained by S-alkylation with acetonitrile. It was noted that the cyano group may not have any role in increase in the activity. When the sulfhydryl group were optimized and investigated, it resulted into the loss of activity.

Xin et al [22] reported sixteen novel oxazolidinone analogue containing substituted thiazole/ fused bicyclic [imidazo[1,2-b] pyradazine/imidazo [2,1-b] thiazole groups were designed and synthesized. All the compounds were evaluated for their in vitro antibacterial activity against S. aureus. Among them compound [14] displayed promising antibacterial activity comparable to that of linezolid.

Vicini et al [23] produced a new set of 2-thiazolylimino-5-arylidene-4-thiazolidinones and assayed in vitro for their antimicrobial activity against Gram positive and Gram negative bacteria, yeast and mould. All the compounds especially compound [15] exhibited potent against Gram positive bacteria. They have studied the structure-activity relationship and found that the 5-arylidene derivatives showed a significant antibacterial efficacy greater than that of the parent compound suggesting that the unsubstituted and substituted 5-arylidene moiety plays an important role in enhancing the antimicrobial properties of this class of compounds.

Dundar et al [24] presented a set of thiazolyl thiazolidine-2,4-dione derivatives and screened them for their antibacterial and antifungal activities against methicillin resistant S. aureus, E. coli and C. albicans. All the compounds particularly [16] were found to be moderately potent against screened microorganisms. The structure-activity relationships showed that the anti-fungal activity of the substituents at the phenyl ring is H, Cl, Br, o,p-diCl > F, NO2 for benzylic 2,4-TZD compounds. As for phenacyl 2,4-TZD compounds, it is Cl, Br > H, F, o,p-di-Cl, NO2.

Cukurovali et al [25] reported a series of Schiff bases containing 2, 4-disubstituted thiazole and cyclobutane rings and hydrazones moieties in the same molecule and evaluated them for antibacterial and antifungal activities. Among the tested compounds, the most effective compound providing a MIC value of 16 μg ml-1 was found to be [17] against C. tropicalis and B. subtilis. They studied the lowest effective substance against all the microorganisms and found that despite all the substances have very similar structures, their antibacterial and antifungal activities are very different. Most of them demonstrate weak activity against gram-positive and gram-negative bacteria and fungi in comparison to the reference drugs.

Zitouni et al [26] reported new thiazole derivatives of triazoles and evaluated for antifungal and antibacterial activity. Their antimicrobial activities against Candida albicans (two strains), C. glabrata, E. coli, S. aureus, P. aeruginosa were investigated. The results showed that some of the compounds [18] have very strong antifungal activity.

Abdel-Wahab et al [27] synthesized a series of 1-(benzofuran-2-yl)-4-nitro-3-arylbutan-1-ones and 3-(benzofuran-2-yl)-4,5-dihydro-5-aryl-1-[4-(aryl)-1,3-thiazol-2-yl]-1H-pyrazoles. All the synthesized compounds were screened for their antibacterial and antifungal activities. Compound [19] showed a significant activity against E. coli higher than that of the control drug, whereas antifungal activity against Aspergillus niger was also exhibited by some of the compounds equal to that of the reference drug.

Karegoudar et al [28] synthesized a series of novel 4-aryl-2-(2, 3, 5-trichlorophenylidenehydrazino)-1, 3-thiazoles in good yield. The newly synthesized compounds were screened for their antibacterial and antifungal activities. Preliminary results reveal that derivatives of synthesized compound [20] are showing promising antimicrobial activity.

.

1.2.4. Antifungal activity

Narayana et al [29] prepared a series of 5-{2-[(N-substituted aryl) amino]-1, 3-thiazol-5-yl} 2-hydroxy benzamides by reacting 5-(bromoacetyl) salicylamide with thiourea, thioformamide, thioalkylamide and substituted thioureas in absolute ethanol. These compounds were converted to 5-(2-substituted–1, 3-thiazol-5-yl)-2-alkoxybenzamides and 5-(2-N-(substituted aryl)-1, 3-thiazol-5-yl)-2-alkoxy benzamides by reacting with n-alkylbromides in presence of a base. The newly synthesized compounds were screened for their antifungal activity. The derivatives of compound [21] exhibited significant activity.

Beuchet et al [30] synthesized polymethoxylated and polyhydroxylated derivatives of 2-amino-4-arylthiazoles bearing a halogenobenzenesulfonamide moiety at position 2 as azole antifungal analogues. In vitro assays against various pathogenic fungal strains (Candida and Trichophyton species) showed no activity in comparison to econazole as reference.

Chimenti et al [31] reported the synthesis of a novel series of 2-thiazolylhydrazone derivatives and the influence of the substituents on the thiazole ring on antifungal activity. All synthesized compounds were screened for their in vitro activities against 22 clinical isolates of Candida sp., representing six different species, compared to clotrimazole as a reference compound. Some of the tested compounds were found to possess significant antifungal activity when compared to clotrimazole, in particular compound [23] which exhibited higher potency against most of the Candida sp. considered. The compounds that were most active as anti-Candida agents were also submitted to cytotoxic screening by the Trypan Blue dye exclusion assay and in general they were shown to induce low cytotoxic effects.

1.2.5. Antitubercular activity

Shiradkar et al [32] synthesized a series of N-{4-[(4-amino-5-sulfanyl-4H-1, 2, 4-triazol-3-yl) methyl]-1, 3-thiazol-2-yl}-2-substitutedamide [24], [25] and [26] derivatives in good yields. The compounds were evaluated for their preliminary