Imidazole as a Promising Medicinal Scaffold: Current Status and Future Direction

Abstract

Various imidazole-containing compounds have been tested for their medical usefulness in clinical trials for several disease conditions. The rapid expansion of imidazole-based medicinal chemistry suggests the promising and potential therapeutic values of imidazole-derived compounds for treating incurable diseases. Imidazole core scaffold contains three carbon atoms, and two nitrogen with electronic-rich characteristics that are responsible for readily binding with a variety of enzymes, proteins, and receptors compared to the other heterocyclic rings. Herein, we provide a thorough overview of the current research status of imidazole-based compounds with a wide variety of biological activities including anti-cancer, anti-microbial, anti-inflammatory and their potential mechanisms including topoisomerase IIR catalytic inhibition, focal adhesion kinase (FAK) inhibition, c-MYC G-quadruplex DNA stabilization, and aurora kinase inhibition. Additionally, a great interest was reported in the discovery of novel imidazole compounds with anti-microbial properties that break DNA double-strand helix and inhibit protein kinase. Moreover, anti-inflammatory mechanisms of imidazole derivatives include inhibition of COX-2 enzyme, inhibit neutrophils degranulation, and generation of reactive oxygen species. This systemic review helps to design and discover more potent and efficacious imidazole compounds based on the reported derivatives, their ADME profiles, and bioavailability scores that together aid to advance this class of compounds.

Keywords:

• imidazole
• apoptosis
• kinase inhibitors
• tubulin polymerization
• topoisomerase II

Acknowledgments

The authors want to express their sincerest gratitude to the College of Pharmacy (COP) at King Saud bin Abdulaziz University for Health Sciences (KSAU-HS) for their continued support.

Abbreviations

A375, Human Melanoma Cells; A549, Lung Cancer Cells; ADME, Absorption, Distribution, Metabolism, and Excretion; ASPC-1, pancreatic cancer cells; B16, Mouse Melanoma Cells; BBB, Blood-Brain Barrier; CDK6, Cyclin-Dependent Kinase 6; CNE-1, Nasopharyngeal Carcinoma; COX-1, cyclooxygenase-1; COX-2, cyclooxygenase-2; CTX, Cyclophosphamide; CYP2C19, Cytochrome P 450 2C19; CYP3A4, Cytochrome P 450 3A4; EAT, Ehrlich Ascites Tumor; EAT, Ehrlich Ascites Tumor; ERs, Estrogen Receptors; ESBL, Extended Spectrum Beta-Lactamases; FAK, Focal Adhesion Kinase; Flavus, Aspergillus flavus; GI, Gastrointestinal; GPCR, G protein Coupled Receptors; GSK-3β, Glycogen Synthase Kinase 3 beta; H. oryzae, Hirschmanniella oryzae; HBA, Hydrogen Bond Acceptor; HBD, Hydrogen Bond Donor; HCT-116, Colon Cancer Cells; HEK 293, Kidney Cancer Cells; HL-60, Human Myeloid Leukemia Cells; HUVECS, Human Umbilical Vein Endothelial Cells; K562, Human Myeloid Leukemia Cells; Log P, Lipophilicity; Log S, Solubility; MCF-7, Breast Cancer Cells; Mcl-1, Myeloid Cell Leukemia 1; MDA-MB-231, Brest; MIC, Minimum Inhibitory Concentration; MPO, myeloperoxidase; MRSA, Methicillin-Resistance Staphylococcus Aureus; MW, Molecular Weight; NCI-60, National Cancer Institute- 60; NF-κB, Nuclear Factor Kappa B Niger, Aspergillus Niger; NSAID, Nonsteroidal Anti-inflammatory Drugs; PANC-1, human pancreatic cancer cell line; PC-3, Prostate Cancer Cells; ROF, Rule of five; ROS, reactive oxygen species; S. Typhimurium, Salmonella typhimurium; SH-SY5Y, Neuroblastoma Cells; SMCS, Smooth Muscle Cells; subtilis, Bacillus subtilis; T. cruzi, Trypanosoma cruzi; T. vaginalis, Trichomonas vaginalis; T. viridae, Trichoderma viridae; U87-MG, Brain Cancer Cells; VRE, Vancomycin-Resistant Enterococci.

Disclosure

The authors declare no conflicts of interest for this work.

Additional information

Funding

The authors acknowledge financial support from King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard Health Affairs, Riyadh, Kingdom of Saudi Arabia. Grant # (SP20.441.R).