Benzimidazole Derivatives in Drug Design: Structure-Activity Relationships and Therapeutic Potential: A Review

Muhammad Tariq Khan; Tayyaba Zulfiqar; Hafsa Jabeen; Nitasha Gohar; Tariq Javed; Zahid Munawar; Muhammad Jawad Hassan; Muhammad Mubashir Rasheed; Eisha Amir

Authors

Muhammad Tariq Khan Department of Pharmacy, Quaid-i-Azam University, Islamabad
Tayyaba Zulfiqar Department of Pharmacy, Quaid-i-Azam University, Islamabad
Hafsa Jabeen Faculty of Pharmacy, Capital University of Science & Technology, Islamabad Expressway, Islamabad
Nitasha Gohar Faculty of Pharmacy, Capital University of Science & Technology, Islamabad Expressway, Islamabad
Tariq Javed Margalla College of Pharmacy, Margalla Institute of Health Sciences, 58001, Rawalpindi
Zahid Munawar Department of Pharmaceutical Sciences, Pak-Austria Fachhochschule, Haripur, KPK
Muhammad Jawad Hassan Faculty of Pharmacy, Capital University of Science & Technology, Islamabad Expressway, Islamabad
Muhammad Mubashir Rasheed Faculty of Pharmacy, Capital University of Science & Technology, Islamabad Expressway, Islamabad
Eisha Amir Faculty of Pharmacy, Capital University of Science & Technology, Islamabad Expressway, Islamabad

Keywords:

Benzimidazole derivatives, Drug design, Heterocyclic compounds, Antioxidants, Anti-inflammatory, Anticancer

Abstract

Benzimidazole, a heterocyclic compound formed by the fusion of benzene and imidazole rings, has become a crucial scaffold in medicinal chemistry due to its versatile pharmacological properties. It plays a key role in the development of antiviral, anticancer, anti-inflammatory, and antiparasitic drugs. The benzimidazole ring is particularly effective in biological and clinical applications because its derivatives, as isosteres of natural nucleotides, can easily interact with biological macromolecules. This review explores the pharmacological activities of benzimidazole derivatives, emphasizing their structural modifications and the mechanisms that drive their therapeutic effects. It highlights their significant potential in modern medicine. Benzimidazole derivatives are known for their anticancer properties due to their resemblance to the nitrogenous base purine, which allows them to exhibit a broad spectrum of biological activities. Complexes of benzimidazole derivatives with copper and zinc, such as complex 1 and 11, respectively, have shown significant interactions with biomolecules, demonstrating nuclease activity and DNA-binding capabilities. Complex 1, in particular, has demonstrated potent cytotoxic activity against human cancer cells, including HepG2, HeLa, and MDA-MB 231, with results comparable to the standard drug, cisplatin. In addition to anticancer effects, benzimidazole derivatives have also shown antioxidant, analgesic, and anti-inflammatory properties. They have been particularly effective in conditions like acute respiratory distress syndrome by decreasing nitric oxide levels and inhibiting the activation of p38 MAPK and NF-κB. This review highlights the latest advancements in benzimidazole research, showcasing its emerging applications in treating protozoal infections, cancer, pain, viral infections, and inflammatory diseases, underscoring its significant role in drug development and its broad therapeutic potential.