Recent Advances in the Anticancer Applications of Benzimidazole Derivatives

Benzimidazole derivatives were first discovered in the late 19th and early 20th centuries, marking a significant milestone in the field of chemistry. These compounds have since played a pivotal role in pharmacology, demonstrating a wide array of pharmacological properties that have had a profound impact on medicine and healthcare. The significance of benzimidazole derivatives in pharmacology is undeniable. These compounds have been extensively studied and developed for their diverse and valuable properties. They exhibit potent anticancer activity, with some derivatives displaying the ability to hinder the growth of cancer cells, offering hope in the fight against this disease. Furthermore, benzimidazole derivatives have been involved in the management of cardiovascular conditions as antihypertensive agents, aiding in the control of high blood pressure. Their potential as antidiabetic agents, by influencing glucose metabolism and insulin secretion, holds promise in diabetes treatment. The recent patent literature has focused on structural modifications to the benzimidazole core to expand the arsenal of effective drugs. This review takes a disease‐centric perspective on patented benzimidazoles from 2016 to 2023. The relevant granted patent applications were located using patent databases, USPTO, Google Patents, EPO, WIPO, Lens and Espacenet.

Synthesis and Pharmacological Properties of the Benzimidazole Scaffold: A Patent Review

Mehra,

Sangwan

2023

Synthesis, Cytotoxic Activity, Docking and MD Simulation ofN,N‐Disubstituted New Benzimidazolium Salts

Mavvaji,

Muhammed,

Akkoc

2023

Self Cite

Novel N,N‐disubstituted benzimidazolium salts were efficaciously synthesized in moderate to high yields and identified via 1H NMR and 13C NMR analyses. These compounds were tested on human liver cancer, prostate cancer, and normal embryonic kidney cell lines for 72 h. The results demonstrated that these compounds had antiproliferative activity. In particular, it was found that one of the compounds, 1‐(3‐chlorobenzyl)‐3‐(3‐methylbenzyl)‐1H‐benzo[d]imidazol‐3‐ium chloride, showed very high activity against liver cancer cell line and the IC50 value of this compound was almost twice as low as the IC50 value of cisplatin. The anticancer activity potential of the compounds was explored through computational methods to support the experimental study results. The binding potential of the compounds to human sulfotransferase 1A1 (SULT1A1) was investigated through molecular docking and molecular dynamics simulation. Their electrochemical properties were computed via density functional theory. The molecular docking study exhibited that 1‐(3‐methylbenzyl)‐3‐(4‐nitrobenzyl)‐1H‐benzo[d]imidazol‐3‐ium chloride had the highest potential to bind to SULT1A1. The molecular dynamics study showed that the synthesized compounds formed a stable complex. Furthermore, the density functional theory study exhibited that 1‐(3‐chlorobenzyl)‐3‐(4‐fluorobenzyl)‐1H‐benzo[d]imidazol‐3‐ium chloride might have the highest chemical stability.

Probing the Adsorption Sites of 5‐amino‐2‐mercaptobenzimidazole Conformations on Colloidal Gold Nanoparticles Investigated by SERS and DFT

Hussain,

Karim,

Pang

2024

Gold nanoparticles (AuNP) have shown great potential in biomedical applications due to their unique and tunable properties. Understanding the ligand conformation on AuNP has profound interest in nanoparticle research leading to a precise drug delivery system. Colloidal AuNPs were synthesized using trisodium citrate as reducing agent. Normal Raman spectrum (NRS) in solid and aqueous phase identifies that 5‐amino‐2‐mercaptobenzimidazole (5A2MBI) mainly exist as thione form. Surface enhanced Raman scattering (SERS) investigation of 5A2MBI depending on pH was performed to explore the adsorption mechanism of thiolate and thione conformations on AuNPs. Density functional theory (DFT) calculations were used to find the band assignments and molecular electrostatic potential (MEP) mapping to identify the electron rich site where metal can interact preferentially. Using SERS spectral analysis and DFT results, surface adsorption scheme was proposed. At basic pH, 5A2MBI adsorbs on AuNP as thiolate form bidentately via Sulfur and nitrogen atom of imidazole ring with tilted geometry. However, in acidic condition the thione form adsorbs on nanosurface with perpendicular orientation.