Recent Advances in Therapeutic Applications of Bisbenzimidazoles

Abstract

Nitrogen-containing heterocycles are one of the most common structural motifs in approximately 80% of the marketed drugs. Of these, benzimidazoles analogues are known to elicit a wide spectrum of pharmaceutical activities such as anticancer, antibacterial, antiparasitic, antiviral, antifungal as well as chemosensor effect. Based on the benzimidazole core fused heterocyclic compounds, crescent-shaped bisbenzimidazoles were developed which provided an early breakthrough in the sequence-specific DNA recognition. Over the years, a number of functional variations in the bisbenzimidazole core have led to the emergence of their unique properties and established them as versatile ligands against several classes of pathogens. The present review provides an overview of diverse pharmacological activities of the bisbenzimidazole analogues in the past decade with a brief account of its development through the years.

Cancer-testis antigen CEP55 serves as a prognostic biomarker and is correlated with immune infiltration and immunotherapy efficacy in pan-cancer

“…We detected possible inhibitors for the regulation of CEP55 expression or the targeting of CEP55-related pathways and confirmed these using molecular docking analyses. Three smallmolecule compounds were identified that had a strong affinity for CEP55: cytochalasin B, which is a G-actin superimposed inhibitor that can suppress the growth of many types of cancer (Croop and Holtzer, 1975); palbociclib, which is a CDK4/6 inhibitor licensed by the FDA for the treatment of ER+, HER2-breast cancer (Konar et al, 2022), and given that CDK4/6 are critical cell cycle regulators, off-target effects of palbociclib on CEP55 may contribute to its efficacy in triggering tumor cell cycle arrest; and bisbenzimide, which is involved in numerous pharmacological actions, including anticancer, antiparasitic, antibacterial, antifungal, antiviral, and chemosensor activities (Verma et al, 2020). However, the exact effects of these three small compounds on CEP55 remain to be further investigated.…”

Studies on anticancer properties with varying co-ligands in a Ru(ii) arene benzimidazole system

“…24,25 The anti-inflammatory, antitumor, antibacterial, antiviral, antiparasitic, and antifungal properties of biologically active benzimidazole-based ligands have been studied extensively since a similar core structure exists in various pharmaceutical compounds. [26][27][28][29][30] Ru(II) complexes using benzimidazole-based ligands like 2-aminophenyl benzimidazole 31 and methyl 1-butyl-2-arylbenzimidazolecarboxylate have been synthesized in the recent past and they show strong binding capabilities with CT-DNA and consequently show strong cytotoxicity against cancer cells. Apart from attacking the DNA in the nucleus, cell death might also be caused due to the production of superoxide anions which induce mitochondrial damage, as reported with a bis-benzimidazole derivative ligand.…”

Influence of Chirality of Benzimidazole Amine Hybrids on Inhibition of Human Erythrocytes Carbonic Anhydrase I, II and Acetylcholinesterase

“…These remarkable structures have tremendous pharmacological activity, including anti‐inflammatory, antiviral, anthelmintic, antihistaminic, antitubercular, antiulcer and antimicrobial, antiprotozoal, antileishmanial, antiglycation and antioxidant, antimycobacterial, anti‐HIV, antitumor, and antiproliferative properties [16–28] . Recently, compounds containing benzimidazole structures have been identified as an anti‐hypertensive agent, novel Zika inhibitors, inhibitors targeting HCV NS5B polymerase, antileukemic agents, potent activators of AMP‐activated protein kinase anti‐hepatitis C, and anticonvulsants [29–35] . Richards et al.…”

“…[16][17][18][19][20][21][22][23][24][25][26][27][28] Recently, compounds containing benzimidazole structures have been identified as an anti-hypertensive agent, novel Zika inhibitors, inhibitors targeting HCV NS5B polymerase, antileukemic agents, potent activators of AMP-activated protein kinase anti-hepatitis C, and anticonvulsants. [29][30][31][32][33][34][35] Richards et al demonstrated that the main benzimidazole structure has good efficacy in treating allergies and asthma. [36] In addition to these studies, various studies have reported that benzimidazole derivatives have anticancer effects.…”