Introduction

Benzimidazole represents a key aromatic heterocyclic organic compound. Over recent decades,
pharmaceutical researchers have been captivated by the synthesis of benzimidazole-derived
poly heterocycles due to their significant role as a pharmacophore in medicinal chemistry and
pharmacology. Essentially, benzimidazole constitutes a bicyclic compound formed by the fusion
of benzene with imidazole, resulting in a structurally privileged framework. This distinctive
structure possesses numerous pharmacological attributes. Notably, the most renowned
benzimidazole moiety to date is N-ribosyl-dimethyl benzimidazole, occurring naturally and
serving as the axial ligand for cobalt in vitamin B [1]

Benzimidazole displays a plethora of biological activities, spanning antimicrobial, antifungal,

antihistaminic, anti-inflammatory, antiviral, antioxidant, anticancer, and anti-ulcerative properties.
This broad spectrum of functions underscores the importance of benzimidazole derivatives in
the development of pharmaceutical compounds with diverse therapeutic applications.[2-3]

The biological relevance of many heterocyclic building blocks lies in their structural similarity to
purine nucleobases. In particular, benzimidazole derivatives exhibit a selective ability to inhibit
endothelial cell growth, thereby exerting a suppressive effect on angiogenesis, both in vitro and
in vivo.[3]

In the 1990s, benzimidazole underwent significant modification, with fluorine, propylene,

tetrahydroquinoline, and cyclized molecules being substituted for various benzimidazole
derivatives. These alterations resulted in the production of compounds characterized by
Enhanced bioavailability, stability, and notable biological activity. Moreover, studies
demonstrated that the addition of an electron-donating group to pyridine contributed to
increased activity. In 1991, advancements allowed for the creation of benzimidazole derivatives
through derivatization at the N-H position with electron-donating groups, accompanied by the
substitution of large chains such as propyl, acetamido, thio, thiazole-amino, and tetramethyl
piperidine on pyridine. These derivatives exhibited potent antiulcer activity. [4-5]

Several attempts have been made in the past to establish an efficient and low-cost process for
the synthesis of benzimidazole derivatives. There are three main techniques for synthesising 2-
substituted benzimidazoles. The first is the Phillips-Ladenburg reaction, which is based on the
relationship of diaminobenzenes with In addition, the second approach involves the
Weidenhagen reaction, which centres on the interaction between ortho-phenylenediamine and
aldehydes or ketones. However, the utilization of these methods in their conventional form is
hindered by the extreme temperature conditions, often ranging from 250 °C to 300 °C, and low
yields. As a result, all currently accessible benzimidazole synthesis techniques are essentially
variations of the Phillips-Ladenburg and Weidenhagen processes. Lastly, the third method,
known as the Mamedov heterocycle rearrangement, entails an acid-catalyzed transformation of
quinoxalinone derivatives into 2-heteroaryl-substituted benzimidazoles [6-7]

Improtance of benzimidazoles in medicinal chemistry

Benzimidazoles display a diverse array of biological functions, rendering them valuable

templates for drug discovery. They have proven effective as antiparasitic agents against various
helminths and protozoa, encompassing nematodes, cestodes, and trematodes. Additionally,
benzimidazoles exhibit antimicrobial properties against bacteria, fungi, and certain viruses.
Furthermore, They demonstrate anticancer activity by targeting crucial cellular pathways
implicated in cancer development.
Given their multifaceted pharmacological attributes, benzimidazoles serve as versatile
frameworks in drug exploration, rendering them indispensable in the search for novel
therapeutic interventions. Their efficacy extends across various therapeutic domains, making
them appealing candidates for treating a wide spectrum of diseases and conditions.[8]
Antiparasitic Activity: In terms of antiparasitic activity, benzimidazoles have long been
acknowledged for their effectiveness against diverse parasitic infections, notably helminths and
protozoa. Benzimidazole medications such as albendazole and mebendazole find extensive use
in treating nematode infections, encompassing intestinal parasites like Ascaris lumbricoides and
hookworms. Moreover, they exhibit efficacy against cestodes and trematodes, offering a
comprehensive approach to managing parasitic diseases.[8]

Antimicrobial Properties: Apart from their effectiveness against parasites, benzimidazoles

also showcase antimicrobial properties against a diverse array of microbial pathogens, spanning
bacteria, fungi, and specific viruses. Their efficacy extends to both gram-positive and
gram-negative bacteria, suggesting potential utility in tackling bacterial infections. Additionally,
benzimidazole derivatives display antifungal activity against various fungal strains, positioning
them as prospective options for treating fungal infections. Moreover, certain benzimidazoles
have shown promise in combating specific viruses, although further research is warranted to
comprehensively understand their mechanisms of action and therapeutic applicability in this
context. [8]

Anticancer Activity: Benzimidazoles are emerging as promising contenders in the fight

against cancer due to their capacity to target critical cellular pathways involved in cancer
advancement. Their anticancer effects operate through diverse mechanisms, such as hindering
microtubule polymerization, disrupting mitotic spindle formation, triggering apoptosis, and
adjusting signaling pathways linked with cell growth and survival. Benzimidazole variations have
demonstrated effectiveness against a broad spectrum of cancer types, spanning solid tumors
and blood-related malignancies, rendering them appealing candidates for further advancement
as anticancer medications. Moreover, their potential for combined therapy with existing
anticancer agents shows potential for augmenting treatment efficacy and surmounting drug
resistance in cancer patients.[8]

Therapeutic Versatility
Benzimidazoles are renowned for their therapeutic versatility, having been harnessed in the
development of drugs targeting a wide spectrum of diseases and conditions. This versatility
stems from their unique chemical structure and diverse pharmacological properties, making
them valuable tools in medicinal chemistry.

Anthelmintic agents: Among their notable therapeutic uses, benzimidazoles are widely
recognized as anthelmintic agents for treating parasitic worm infections. Albendazole and
mebendazole, two prominent derivatives, play pivotal roles in helminthiasis management by
targeting various parasitic worms like nematodes, cestodes, and trematodes.[9]

Their effectiveness in eradicating intestinal parasites and curbing disease spread has solidified
their status as vital elements in public health initiatives striving to control parasitic infections,
particularly in regions with limited resources.
Antimicrobial Properties: Benzimidazole-based antibiotics represent another dimension of the
therapeutic versatility offered by benzimidazoles. Compounds like thiabendazole showcase
robust antimicrobial properties against a wide range of microbial pathogens, encompassing
bacteria, fungi, and specific parasites. For instance, thiabendazole has shown effectiveness
against bacterial strains such as Staphylococcus aureus and Streptococcus species, along with
fungal pathogens like Candida albicans. Its broad-spectrum antimicrobial activity positions it as
a valuable tool in treating infectious diseases, especially those triggered by multidrug-resistant
pathogens.[9]

Triazole

N-heterocyclic compounds are plentiful in nature and serve vital functions in various
physiologically significant compounds like vitamins, nucleic acids, pharmaceuticals,
dyes, and agrochemicals. They are widely recognized within the domains of organic and
medicinal chemistry, both of which are experiencing rapid expansion, as well as in the
pharmaceutical sector.(1–7).
Reference

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