Imidazole and its Biological Activities: A Review

 

U. Sahoo¹*, S. Biswal¹, S. Sethy¹, H.K.S. Kumar¹ and M. Banerjee¹

Department of Medicinal Chemistry, Institute of Pharmacy and Technology, Salipur, Cuttack, Odisha-754202

^*Corresponding Author E-mail: uks1998@gmail.com

ABSTRACT:

Imidazole is a planer five-member heterocyclic ring with 3C and 2N atom and in ring N is present in 1st and 3rd positions. The imidazole ring is a constituent of several important natural products, including purine, histamine, histidine and nucleic acid. Being a polar and ionisable aromatic compound, it improves pharmacokinetic characteristics of lead molecules and thus used as a remedy to optimize solubility and bioavailability parameters of proposed poorly soluble lead molecules. Imidazole derivatives have occupied a unique place in the field of medicinal chemistry. The incorporation of the imidazole nucleus is an important synthetic strategy in drug discovery. The high therapeutic properties of the imidazole related drugs have encouraged the medicinal chemists to synthesize a large number of novel chemotherapeutic agents. Imidazole drugs have broadened scope in remedying various dispositions in clinical medicines. Numerous methods for the synthesis of imidazole and also their various structure reactions offer enormous scope in the field of medicinal chemistry. This articles aims to review the work reported, their chemistry and biological activities of imidazole during past years.

 

 

 

INTRODUCTION:

Medicinal chemistry is the discipline concerned with determing the influence of chemical structure on biological activity and in the practice of medicinal chemistry developed from an empirical one involving organic synthesis of new compound based largely on the modification of structure and then identifies their biological activity . Medicinal chemistry concerns with the discovery, development, interpretation and the identification of mechanism of action of biologically active compounds at the molecular level. Various biologically active syntheticcompounds have five-membered nitrogen-containing heterocyclic ring in their structures [1-4].

 

Structural frameworks have been described as privileged structures and in particular, Ncontaining polycyclic structures have been reported to be associated with a wide range of biological activity. In the field of five membered heterocyclic structures imidazole nucleus shows various properties. The high therapeutic properties of the imidazole related drugs have encouraged the medicinal chemists to synthesize a large number of novel chemotherapeutic agents.

 

Imidazole drugs have broadened scope in remedying various dispositions in clinical medicines. Medicinal properties of imidazole include anticancer, b-lactamase inhibitors, 20- HETE (20-Hydroxy-5,8,11,14-eicosatetraenoic acid) synthase inhibitors, carboxypeptidase inhibitors, hemeoxygenase inhibitors, antiaging agents, anticoagulants, anti-inflammatory, antibacterial, antifungal, antiviral, antitubercular, antidiabetic and antimalarial [5-18]. This group presents in azoles antifungal which inhibit the accumulation of methylated sterols distroy the composition of the lipid bilayer of membranes. Some imidazole drugs, at high concentrations, could exert direct inhibitory action on membranes, without interference with sterols and sterol esters [19, 20]. Infectious microbial disease causes worldwide problem, because microbes have resisted prophylaxis or therapy longer than any other form of life. In recent decades, problems of multidrug-resistant microorganisms have reached an alarming level in many countries around the world. Resistance of anti-microbial agents such as β-lactam antibiotics, macrolides, quinolones and vancomycin etc. and different species of bacteria causes increased important global problem [21]. Imidazole and its derivatives are reported to be physiologically and pharmacologically active and find applications in the treatment of several diseases.

 

Structure and pharmacological activities

Imidazoles are well known heterocyclic compounds which are common and have important feature of a variety of medicinal agents. Imidazole is a 5-membered planar ring, which is soluble in water and other polar solvents. It exists in two equivalent tautomeric forms because the hydrogen atom can be located on either of the two nitrogen atoms. It is a highly polar compound, as evidenced by a calculated dipole of 3.61D, and is entirely soluble in water. The compound is classified as aromatic due to the presence of a sextet of π-electrons, consisting of a pair of electrons from the protonated nitrogen atom and one from each of the remaining four atoms of the ring. Imidazole is amphoteric, i.e. it can function as both an acid and as a base. On the basis of various literature surveys Imidazole derivatives shows various pharmacological activities

_ Anti fungal and Anti-bacterial activity

_ Anti inflammatory activity and analgesic activity

_ Anti cancer activity

_ Anti viral activity

 

·      Anti amoebic activity

·      Antiglaucoma activity

·      Antihypertensive activity

·      Antihistamine activity

·      Antiepileptic activity

·      Antithyroid activitya

·      Nasaldecongestants

 

Given below is a brief account of various alterations conducted on imidazole ring containing few inportent marketed drug and their associated biological activities.

 

 

Table: imidazole ring containing few marketed drug shows various biological activities

NAME OF DRUGS	STRUCTURE AND NOMENCLATURE	USE	REFERENCE
MICONAZOLE-		ANTIFUNGAL AGENT	Pandeya S.N.et.al.22
KETOCONAZOLE-		ANTIFUNGAL AGENT	Pandeya S.N.et.al.23.
CLOTRIMAZOLE-		ANTIFUNGAL AGENT	Pandeya S.N.et al.23.
DACARBAZINE-		ANTICANCER AGENT	Pandeya S.N.et.al.23.
MERCAPTOPURINE-         THIOGUANINE-		ANTICANCER AGENT       ANTICANCER AGENT	Pandeya S.N.et.al.23.     Lennard L.et.al.32.
OXALIPLATIN-                     ORMAPLATIN-		ANTICANCER AGENT           ANTICANCER AGENT	Bothara K.G.et.al.25.         Bothara K.G.et.al.25
ACYCLOVIR-                                 VALACICLOVIR-	2-[(2-amino-1,6,7,8-tetrahydro – 9H-purin-9-yl)methoxy]ethyl 2-amino-3-methylbutanoate	ANTIVIRAL AGENT                             ANTIVIRAL AGENT	Pandeya S.N.et.al.23                           Valentina.et.al.28
GANCICLOVIR-		ANTIVIRAL AGENT	Pandeya.S.N.et.al.23
CARBOVIR-	2-amino-9-[2-(hydroxymethyl)cyclopent-3-en-1-yl]-1-9-dihydro-6H-purin-6-one	ANTI-HIV AGENT	Pandeya.S.N.et.al.23
METRONIDAZOLE-                                   TINIDAZOLE-		ANTIAMOEBIC AGENT                               ANTIAMOEBIC AGENT	Pandeya.S.N.et. al.23                               Pandeya.S.N.et.al.23
ORNIDAZOLE-           NIMORAZOLE-		ANTIAMOEBIC AGENT     ANTIAMOEBIC AGENT	Pandeya.S.N.et.al.23       Pandeya.S.N.et.al.23
PILOCARPINE-		ANTIGLAUCOMA AGENT	Gokhle.S.B.et.al.30
BURIMAMIDE-                   METIAMIDE-		H2 BLOCKER                 H2 BLOCKER	Bothara.K.G.et.al.26.                 Bothara S.B.et.al.26
PHENYTOIN-               MEPHENYTOIN-		ANTIEPILEPTIC AGENT       ANTIEPILEPTIC AGENT	Pandeya S.N.et.al.22             Pndeya S.N.et.al.22
ETHOTOIN-     -           ALBUTOIN-		ANTIEPILEPTIC AGENT             ANTIEPILEPTIC AGENT	Pandeya S.N.et.al.22               Pandeya S.N.et.al.22
SULMAZOLE-                 CLONIDINE-		ANTIHYPERTENSIVE AGENT           ANTIHYPERTENSIVE AGENT	Pandeya S.N.et.al.22.             Pandeya S.N.et.al.22.
TRIAMENIDINE-             TOLAZOLINE-		ANTIHYPERTENSIVE AGENT         ANTIHYPERTENSIVE AGENT	Pandeya S.N.et,al.22           Pndeya S.N.et.al.22
METHIMAZOLE-                         CARBIMAZOLE-		ANTITHYROID AGENT                   ANTITHYROID AGENT	Pandeya S.N.et.al.23                   Pndeya S.N.et.al,23
XYLOMETAZOLINE-                         NAPHAZOLINE-                           TETRAHYDROZOLINE-		NASAL DECONGESTANT                     NASAL DECONGESTANT                       NASAL DECONGESTANT	Kar Asutosh. et.al.24                   Kar Asutosh. et.al.24.                         Kar Asutosh. et.al.24.
PANTOPRAZOLE-                                 TIMOPRAZOLE-                     PICOPRAZOLE-	5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole     Methyl 6-methyl-2-{[3-methylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole-5-carboxylate	PROTONPUMP INHIBITOR                             PROTONPUMP INHIBITOR                 PROTONPUMP INHIBITOR	Sriram D.et.al.29.                             Bothara K.G.et.al.26                 Bothara K.G.et.al.26
PIROXIMONE-                                         FEROXIMONE-	4-methyl-5-{[4-(methylsulfanyl)phenyl]carbonyl}-1,3-dihydro-2H-imidazol-2-one	ANTI-CHF AGENT                                     ANTI-CHF AGENT	Pandeya S.N.et.al.22                                     Pandeya S.N.et.al.22
ALINIDINE-                                                         THEOPHYLLINE-                       THEOBROMINE-	N-(2,6-dichlorophenyl)-N-(prop-2-en-1-yl)-4,5-dihydro-1H-imidazol-2-amine	ANTI-ARRYTHMIA AGENT                                                   ANTIASTHMATIC AGENT                     ANTIASTHMATIC AGENT	Pandeya S.N.et.al.22                                                     Tripathi K.D.et.al.31.                     Tripathi K.D.et.al.31.
CAFFEINE-		ANTIASTHMATIC AGENT	Tripathy K.D.et.al.31.
DYPHYLLINE-	7-(2,3-dihydroxypropyl)-1,3-dimethyl-3,4,5,7-tetrahydro-1H-purine-2,6-dione	ANTIASTHMATIC AGENT	Pandeya S.N.et.al.22.
ETOPHYLLINE-	7-(2-hydroxyethyl)-1,3-dimethyl-3,4,5,7-tetrahydro-1H-purine-2,6-dione	ANTIASTHMATIC AGENT	Kar Asutosh.et.al.24.
PROXYPHYLLINE-	7-(hydroxypropyl)-1,3-dimethyl-3,4,5,7-tetrahydro-1H-purine-2,6-dione	ANTIASTHMATIC AGENT	Pandeya S.N.et.al.22
PENTOXYPHYLLINE-	3,7-dimethyl-1-(4-oxopentyl)-3,4,5,7-tetrahydro-1H-purine-2,6-dione	ANTIASTHMATIC AGENT	Pandeya S.N.et,al.22
MEBENDAZOLE-             ETIBENDAZOLE-	Methyl[6-(2-phenyl-1,3-dioxdan-2-yl)-1H-benzimidazol-2-yl]carbamate	ANTHELMINTIC             ANTHELMINTIC	Kar Asutosh. et.al.24.           Pandeya S.N.et.al.23
LEVAMISOLE-                                 TETRAHYDROZOLINE-                 CLEMIZOLE-		ANTHELMINTIC                                 NASAL DECONGESTANT             ANTIALLERGIC AGENT	Pandeya S.N.et.al.23                               Martindale.et. al.27               Martindale.et. al.27                 .

 

CONCLUSION:

The reviewed imidazole moiety has shown a wide spectrum of biological activities. The various substituted imidazole and are having significant antifungal activity. Significant , antiviral and anti asthmatic activity is displayed by some effective substituted imidazole derivative which presently leading drug in the market in entire. some modified imidazole  are found to to be effective as anti-hypertensive, whereas some of the  derivatives of imidazoles are found to show the anti-asthmatic, anti;viral as special anti HIV action. Recently it was proven that, some of the important marketed imidazole nucleous containing drug having different biological or pharmacological activity were discussed in table. The imidazole nucleous based pharmaceutical are rapidly becoming very important class of therapeutic agents and are likely to replace many existing organic based pharmaceuticals in the very near future. The imidazole based pharmaceuticals will be produced on a large scale by modern drug Discovery Company by different research development processes and will become available commercially for therapeutic use. With the key benefits including favorable time to market and high rate of success in clinical trial compared with traditional pharmaceuticals due to diverse biological action with less toxicity, so in future therapeutic indole drug will play a pivotal role in the treatment of different diseases. The biological profiles of this new generation of imidazole represent much progress with regard to the older compounds.

 

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Received on 18.12.2011         Modified on 15.01.2012

Accepted on 28.01.2012         © AJRC All right reserved