Pharmacological Activities of Benzimidazole Derivatives - An Overview

 

Rohit Tripathi,* Arvind Kumar Singh, Vipul Singh, Preety Mishra, Roopesh Maurya

Kamla Nehru Institute of Management & Technology (Faculty of Pharmacy, Department of Pharmaceutical Chemistry), Faridipur, Sultanpur, Uttar Pradesh, India

*Corresponding Author E-mail:

Benzimidazole derivates play vital role in biological field such as antimicrobial, antiviral, antidiabetic, and anticancer activity.  Therapeutic Significance of these clinically useful drugs in treatment of microbial infections encouraged the development of some more potent and significant compounds. Benzimidazoles are remarkably effective compounds both with respect to their bacteria inhibitory activity and their favorable selectivity ratio. Extensive biochemical and pharmacological studies have confirmed that these molecules are effective against various strains of microorganisms. This comprehensive overview summarizes the chemistry of different derivatives of substituted benzimidazole along with their antimicrobial activity.

 

 

 

INTRODUCTION:

Benzimidazole derivatives are of wide interest because of their diverse biological activity and clinical applications, they are remarkably effective compounds both respect to their inhibitory activity and their favorable selectivity ratio.^2,3 Benzimidazoles are regarded as a promising class of bioactive  heterocyclic compound  that exhibit a range of biological activities. Specifically, this nucleus is a constituent of vitamin- B₁₂.^2,4 The most prominent benzimidazole compound in nature is N-ribosyl-dimethylbenzimidazole, which serve as an axial ligand for cobalt in vitamin B₁₂.⁵ Benzimidazoles and its derivatives have been reported to be physiologically and pharmacologically  active. They have been showing promising  activities in the treatment of several diseases like epilepsy, diabetes and  antifertility.^6,7 For these reasons, they gained much attention as important moiety in medicinal chemistry and including biological activities as antibacterial, antiparasitic agent, antiulcerative, antioxidant, auticonvulsant, antihistamine, anti-inflammatory, antifungal, antihypertensive, antineoplastic, antitubercular, anti-HIV, anti-herpes (HSV-I) and for the treatment of Hepatitis  C and B viruses^8,1.

 

Substitution on Benzimidazole nucleus and their pharmacological activities

The various benzimidazole derivatives were synthesized 1990, with substitution of fluorine, propylene, tetrahydroquinoline and cycles compound which resulted in compounds with increased stability, bioavailability and significant biological activity^7,9.  2-Substituted benzimidazole derivatives have been found to be biologically most potent.¹ In last decades, heterocyclic benzimidazole, their derivatives and metal complexes have received considerable attention in co-ordination chemistry, because of their well documented biological activities. Zinc(II) complex with 1- benzylbenzimidazole  derivatives showed more effective antimicrobial activity.¹⁰ a new series of 5-substituted benzimidazoles holding cyclohexyl or cyclopentyl moieties at position 2 was  synthesized in order determine their antimicrobial activities and feasible structure activity relationships. In 2002 benzimidazole derivative were synthesized by 2-thioalkyl and thioaryl substitution resulting in good antiprotozoal and antibacterial activity.¹¹ In 2006 a series of non peptide angiotensine (A-II) receptor antagonist i.e. 5-substituted (amino) -2- phenyl -1- (2' corboxyphenyl - 4 - yl) benzimidazole were synthesized which produce a potent hypertensive effect upon oral administration¹². Some oxadiazole -1H - benzimidazole has been reported to possess antimicrobial activities. The compound also showed moderate antifungal activity¹³.

The possible substitution at different position of the benzimidazole nucleus is a small substitution on 2^nd and 5^th position of benzimidazole is characteristics for

 

antihelmentic activity where as bulky substitution on 2^nd position showed proton pump inhibitory and antihistaminic activity¹⁴.

 

 

Compound Structure	Derivatives	Pharmacological activity
2- substituted benzimidazole	R=	Antimicrobial  Activity15
	R1 = R2 = R3 = - CH3 - H -NO2 - CH3 - OH - H -CHCH -OH - H -CH2C6H5NO2 -H -NO2	Antimicrobial Activity 16
	R = H, OCH3, OCHF2 n= 2 or 3	Antimicrobial Activity17
	R = -         C6H5NO2 -         C6H5CH3 -         C6H5OCH3	Antimicrobial  Activity18

 

 

	R1 = R2 = R3 = H H H H Cl H H OH H OCH3 OCH3 H	Antimicrobial Activity19
	R1 = CH3, C6H5 R2 = CH3, C6H5 R3 = H, CH3, C6H5	Antimicrobial Activity20
	R= -         C6H5 -         NO2C6H4 4 - OCH3C6H4	Antimicrobial Activity21
	R1  =   R2 = m - Cl NH2 m - F NH2	Antimicrobial Activity22
		Antimicrobial Activity23
	R =	Antimicrobial Activity23
		Antimicrobal Activity24
		Anthelmintic Antifungal Antimicrobial Activities25
	1. R:CH2 = CHCH2     X:Br 2. R:CH2CH = CHC6C5     X:Cl 3. R:Furfural     X:Cl 4. R: Thenyl     X:Cl	Antibacterial Antifungal Activities26
	Ar = 3 - Pyridyl 2 - thienyl	Antibacterial Activity27
	R =                        H 2 - OH 3 - NO2 4 - OH 3 - OCH3 4 - OCH3	Antibacterial Activity28
	R =                        H 2 - OH 3 - NO2 4 - OH 3 - OCH3                        4 - OCH3	Antibacterial Activity28
	Mt Cu2+, Ni2+, Co2+ Zn2+, Mn2+,Fe3+	Antibacterial Activity29
	R = 2 - methyl 2 - benzyl 2 - phenyl	Anthelmintic Activity30
	R X H H 4-NO2 CH3 3-NO2 C2H5 4-Cl C3H7 4-Br   4-CH3   4-CH3	Antibacterial Antifungal Antitubercular Activities31
	R=                     H                     p-CH3                     m-CH3                     m-NO2                     o-Br                     p-Cl                     m-Cl                     COOH	Antibacterial Antifungal Activities32
		Antibacterial  Antifungal Activities33
	R = H 4 - CH3 4 - Cl 4 - NO2 4 - C2H5	Antibacterial Antifungal Activities34
	R1 = R2 = R3 = H H H H Cl H H OH H OCH3 OCH3 H	Anti-inflammatory Activity35
	R =	Anti-Inflammatory Antidepressant Activities36
		Anti-inflammatory Activity37
	R =  = 2,3,4,6,7	Antiallergic Activity38
	R1 = R2 = H methyl H ethyl H propyl NO2 methyl NO2 ethyl NO2 propyl	Antiulcer Antisecretory Activities39
	R = Phenyl 4 - chlorophenyl 4 - methoxyphenyl 4 - bromophenyl 4 - fluorophenyl	Antitubercular Activity40
	R = Phenyl 4 - chlorophenyl 4 - methoxyphenyl 4 - bromophenyl 4 - fluorophenyl	Antitubercular Activity40
	R = cl 4 -  morpholinyl 1 - Pyrrolidinyl 3 - methylpiperidin - 1 - yl	Antifungal Activity41
	R1 = R2 = NO2 Phenyl NH2 ethyl	Antihypertensive Activity42
		Antidiabetic Activity43
		Anticonvulsant Activity43

 

 

CONCLUSION:

According to the literature survey of benzimidazole derivatives shows that 2 - substituted ones are found to be more pharmacologically potent comparison to among benzimidazoles derivatives and synthesis of 2 - substituted benzimidazoles are the potential area of research.This approach noticed so far, that modification on benzimidazole moiety displayed valuable biological actions.

 

The benzimnidazole ring is an important pharmacophore in modern drug discovery. In recent years, attention has increasingly been given to the synthesis of benzimidazole derivatives as a source of new antimicrobial agents. The synthesis of novel benzimidazole derivatives remains a main focus of medicinal research. Recent observation suggest that substituted benzimidazoles and heterocycles, which are the structural isosters of nucleotides owing  fused hetero cyclic nuclei in their  structures that allow them to interact easily with the biopolymer's, Possess potential activity with lower toxicities in the chemotherapeutic approach in man. Since now, researchers have been attracted towards designing more potent benzimidazole derivatives having wide diverse of biological activity.

 

ACKNOWLEDGEMENT:

The author are thankful for the guidance and authorities of Prof. Dr. R. Parthasarathy, Director, and Dr. Arvind Kumar Singh (H.O.D.), Pharmaceutical chemistry, Kamla Nehru Institute of Management and Technology, Faridipur, Sultanpur, Uttar Pradesh  for providing library and laboratory facilities.

 

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Received on 08.04.2013       Modified on 19.04.2013

Accepted on 30.04.2013      © AJRC All right reserved