Synthesis and Pharmacological Profile of Benzimidazoles

Abstract

Benzimidazoles are a class of heterocyclic, aromatic compounds which share a fundamental structural characteristic of six-membered benzene fused to fivemembered imidazole moiety. Molecules having benzimidazole motifs showed promising application in biological and clinical studies. Nowadays it is a moiety of choice which possesses many pharmacological properties extensively explored with a potent inhibitor of various enzymes involved in a wide range of therapeutic uses which are antidiabetic, anticancer, antimicrobial, antiparasitic, analgesics, antiviral, and antihistamine, as well as used in cardiovascular disease, neurology, endocrinology, ophthalmology, and more. The increased interest for benzimidazole compounds has been due to their excellent properties, like increased stability, bioavailability, and significant biological activity. This book chapter mainly discussed recent synthetic methods developed for the benzimidazole derivatives and their pharmacological properties exemplified on several derivatives.

Recent Developments of Target-Based Benzimidazole Derivatives as Potential Anticancer Agents

“…Zhang et al have synthesized a series of 1,2-diarylbenzimidazole derivatives and reported as potential anticancer agents. Among all, the target molecule (12) has been found to show significant cytotoxicity against human cancer cells such as A549, HepG2, HeLa, and MCF-7 cells in the range of GI 50 = 0.71-2.41 μM and also found to show normal cytotoxicity toward normal cells. The apoptosis process by the target compound was confirmed by morphological changes on HepG2 and HeLa-treated cells like cell wall deformation, blebbing, and cell shrinkage, based on apoptosis studies such as mitochondrial membrane potential, annexin V/propidium iodide dual staining assay, and dichlorofluorescein (DCF) fluorescence studies.…”

“…The benzimidazole derivatives (14) were synthesized under mild conditions with inherently low cost by many researchers using (8), (9), (10), (11), (12), and (13), as reactants (Figure 9). Suheyla et al demonstrated the synthesis of benzimidazoles by condensation of O-phenylene diamine with an appropriate aldehyde (8) in the presence of sodium metabisulfite.…”

“…Mahesh et al developed a method of one-pot, multicomponent reaction, which enables the transformation of commercial aryl amines, aldehydes, and azides (11) into various benzimidazoles via an efficient copper-catalyzed amination of N-aryl imines [64]. Lin et al developed a method for solvent/oxidant-switchable synthesis of multisubstituted benzimidazoles via metal-free selective oxidative annulation of arylamidines [65] (12). Wray et al synthesized various N-aryl-1H-indazoles and benzimidazoles from common arylamino oximes (13) in good to excellent yields [66].…”

“…It is among the top five most common five-membered aromatic nitrogen heterocycles in U.S. FDA-approved pharmaceutical drugs [10]. Benzimidazoles are structural isosteres of nucleobases due to the fused nitrogen nuclei and they readily interact with biomolecular targets and elicit many biological activities such as anticancer [11], anti-inflammatory [12], antiulcer [13], anti-hypertensive [14], and anthelmintic [15]. Akhtar et al in his recent review described the therapeutic evolution of benzimidazole scaffolds during the last quinquennial period [16].…”

Potential Hexokinase II Inhibition by Benzimidazole Anthelmintics: Albendazole, Mebendazole and Fenbendazole

“…Although benzimidazoles are primarily utilized as anthelmintic drugs, they have also presented strong therapeutic application against pathogenic bacteria and fungi [5]. Benzimidazole derivatives are also associated with a variety of types of pharmacological activities such anti-inflammatory [6], antiulcer [7], anti-hypertensive [8] and even possibly anticancer [9].…”