Recent Progress of Benzimidazole Hybrids for Anticancer Potential

Abstract

: This review presented the detailed account of factors leading to cancer and design strategy for the synthesis of benzimidazole derivatives as anticancer agents. The recent survey for cancer treatment in Cancer facts and figures 2017 American Chemical society has shown progressive development in fighting cancer. Researchers all over the world in both the developed and developing countries are in continous effort to tackle this serious concern. Benzimidazole and its derivatives showed a broad range of biological activities due to their resemblance with natuarally occurring nitrogenous base i.e purine. The review discussed about benzimidazole derivatives showing anticancer properties through different mechanism viz. intercalation, alkylating agents, topoisomerases, DHFR enzymes and tubulin inhibitors. Benzimidazole derivatives act through different mechanism and the substituents reported from the earlier and recent research articles are prerequisites for synthesis of targeted based benzimidazole derivatives as anticancer agents. The review focuses on easy comparison of the substituent essential for potency and selectivity through SAR presented in figures. This will further provide better outlook or fulfills the challenges faced in the development of novel benzimidazole derivatives as anticancer.

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

“…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.…”

“…Nale et al developed a method for the synthesis of benzimidazole derivatives in the presence of zinc catalysts from N-substituted formamides and various o-phenylenediamines [64] (10). 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).…”

“…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].…”

Dinuclear copper(II) complex with a benzimidazole derivative: Crystal structure, theoretical calculations, and cytotoxic activity

“…enviradine), and antihypertensives (e.g. candesartan and telmisartan) . Besides the pharmacological activities already mentioned, several studies demonstrated that benzimidazole derivatives also possess antitumoral and other relevant biological activities …”

A nanoscopic icosahedral {Mo72Fe30} cluster catalyzes the aerobic synthesis of benzimidazoles

“…1,2 Benzimidazole and its derivatives are an important and promising class of N-heterocycles due to their diverse biological activities and pharmacological properties. 3 Extensive interest in benzimidazole-containing structures has led to wide studies for their synthesis. Three methods have been reported for the synthesis of these compounds including (i) condensation of o-phenylenediamines with carboxylic acids and their derivatives (imidates, nitriles, or orthoesters) which oen requires high reaction temperatures and strong acidic conditions, 4 (ii) transition-metal catalyzed coupling reactions to create the benzimidazole nucleus, 5 and (iii) the condensation of o-phenylenediamine with aldehydes, 6 which has been extensively used due to the accessibility of a large number of aldehydes although it requires a stoichiometric oxidant for dehydration.…”