Synthesis and Biological Evaluation of Novel Imidazole Derivatives As Antimicrobial Agents

Overview

Journal Biomolecules

Publisher MDPI

Specialties Biochemistry
Molecular Biology

Date 2024 Sep 28

PMID 39334964

Authors

Huda A Al-Ghamdi

Fahad A Almughem

Manal A Alshabibi

Abrar A Bakr

Abdullah A Alshehri

Alhassan H Aodah

Nourah A Al Zahrani

Essam A Tawfik

Laila A Damiati

Affiliations

Soon will be listed here.

Abstract

Imidazole derivatives are considered potential chemical compounds that could be therapeutically effective against several harmful pathogenic microbes. The chemical structure of imidazole, with a five-membered heterocycle, three carbon atoms, and two double bonds, tends to show antibacterial activities. In the present study, novel imidazole derivatives were designed and synthesized to be evaluated as antimicrobial agents owing to the low number of attempts to discover new antimicrobial agents and the emerging cases of antimicrobial resistance. Two imidazole compounds were prepared and evaluated as promising candidates regarding in vitro cytotoxicity against human skin fibroblast cells and antimicrobial activity against several bacterial strains. The synthesized imidazole derivatives were chemically identified using nuclear magnetic resonance (NMR) and Fourier-transform infrared spectroscopy (FTIR). The results demonstrated a relatively high cell viability of one of the imidazole derivatives, i.e., HL2, upon 24 and 48 h cell exposure. Both derivatives were able to inhibit the growth of the tested bacterial strains. This study provides valuable insight into the potential application of imidazole derivatives for treating microbial infections; however, further in vitro and in vivo studies are required to confirm their safety and effectiveness.

References

Raghu M, Pradeep Kumar C, Yogesh Kumar K, Prashanth M, Alshahrani M, Ahmad I . Design, synthesis and molecular docking studies of imidazole and benzimidazole linked ethionamide derivatives as inhibitors of InhA and antituberculosis agents. Bioorg Med Chem Lett. 2022; 60:128604. DOI: 10.1016/j.bmcl.2022.128604. View

Wang Z, Zhang Y, Pinkas D, Fox A, Luo J, Huang H . Design, Synthesis, and Biological Evaluation of 3-(Imidazo[1,2- a]pyrazin-3-ylethynyl)-4-isopropyl- N-(3-((4-methylpiperazin-1-yl)methyl)-5-(trifluoromethyl)phenyl)benzamide as a Dual Inhibitor of Discoidin Domain Receptors 1 and 2. J Med Chem. 2018; 61(17):7977-7990. PMC: 6287892. DOI: 10.1021/acs.jmedchem.8b01045. View

Ghannoum M, Rice L . Antifungal agents: mode of action, mechanisms of resistance, and correlation of these mechanisms with bacterial resistance. Clin Microbiol Rev. 1999; 12(4):501-17. PMC: 88922. DOI: 10.1128/CMR.12.4.501. View

Yang X, Song X, Banerjee S, Li Y, Byun Y, Liu G . Developing imidazoles as CEST MRI pH sensors. Contrast Media Mol Imaging. 2016; 11(4):304-12. PMC: 5201433. DOI: 10.1002/cmmi.1693. View

Gratal P, Arias-Perez M, Gude L . 1H-imidazo[4,5-f][1,10]phenanthroline carbohydrate conjugates: Synthesis, DNA interactions and cytotoxic activity. Bioorg Chem. 2022; 125:105851. DOI: 10.1016/j.bioorg.2022.105851. View

Volkov M, Novikov A, Grigoriev M, Fedoseev A, German K . Novel Synthesis Methods of New Imidazole-Containing Coordination Compounds Tc(IV, V, VII)-Reaction Mechanism, Xrd and Hirshfeld Surface Analysis. Int J Mol Sci. 2022; 23(16). PMC: 9408894. DOI: 10.3390/ijms23169461. View

Jun J, Yang S, Lee J, Moon H, Kim J, Jung H . Discovery of novel imidazole chemotypes as isoform-selective JNK3 inhibitors for the treatment of Alzheimer's disease. Eur J Med Chem. 2022; 245(Pt 1):114894. DOI: 10.1016/j.ejmech.2022.114894. View

Kim H, Gu L, Yeo H, Choi U, Lee C, Yu H . Rapid Assembly of Pyrrole-Ligated 1,3,4-Oxadiazoles and Excellent Antibacterial Activity of Iodophenol Substituents. Molecules. 2023; 28(8). PMC: 10142073. DOI: 10.3390/molecules28083638. View

Lee Y, Tan Y, Oon C . Benzimidazole and its derivatives as cancer therapeutics: The potential role from traditional to precision medicine. Acta Pharm Sin B. 2023; 13(2):478-497. PMC: 9978992. DOI: 10.1016/j.apsb.2022.09.010. View

10.

Zhou J, Cai Y, Liu Y, An H, Deng K, Ashraf M . Breaking down the cell wall: Still an attractive antibacterial strategy. Front Microbiol. 2022; 13:952633. PMC: 9544107. DOI: 10.3389/fmicb.2022.952633. View

11.

Tran T, Henary M . Synthesis and Applications of Nitrogen-Containing Heterocycles as Antiviral Agents. Molecules. 2022; 27(9). PMC: 9101374. DOI: 10.3390/molecules27092700. View

12.

SAWYER P, Brogden R, Pinder R, Speight T, Avery . Clotrimazole: a review of its antifungal activity and therapeutic efficacy. Drugs. 1975; 9(6):424-47. DOI: 10.2165/00003495-197509060-00003. View

13.

Atia A . Synthesis and antibacterial activities of new metronidazole and imidazole derivatives. Molecules. 2009; 14(7):2431-46. PMC: 6254976. DOI: 10.3390/molecules14072431. View

14.

Ali I, Lone M, Aboul-Enein H . Imidazoles as potential anticancer agents. Medchemcomm. 2018; 8(9):1742-1773. PMC: 6084102. DOI: 10.1039/c7md00067g. View

15.

Demchenko S, Lesyk R, Zuegg J, Elliott A, Fedchenkova Y, Suvorova Z . Synthesis, antibacterial and antifungal activity of new 3-biphenyl-3H-Imidazo[1,2-a]azepin-1-ium bromides. Eur J Med Chem. 2020; 201:112477. DOI: 10.1016/j.ejmech.2020.112477. View

16.

Balandis B, Mickevicius V, Petrikaite V . Exploration of Benzenesulfonamide-Bearing Imidazole Derivatives Activity in Triple-Negative Breast Cancer and Melanoma 2D and 3D Cell Cultures. Pharmaceuticals (Basel). 2021; 14(11). PMC: 8625351. DOI: 10.3390/ph14111158. View

17.

Alghamdi S, Suliman R, Almutairi K, Kahtani K, Aljatli D . Imidazole as a Promising Medicinal Scaffold: Current Status and Future Direction. Drug Des Devel Ther. 2021; 15:3289-3312. PMC: 8329171. DOI: 10.2147/DDDT.S307113. View

18.

Aliwaini S, Awadallah A, Morjan R, Ghunaim M, Alqaddi H, Abuhamad A . Novel imidazo[1,2-a]pyridine inhibits AKT/mTOR pathway and induces cell cycle arrest and apoptosis in melanoma and cervical cancer cells. Oncol Lett. 2019; 18(1):830-837. PMC: 6540349. DOI: 10.3892/ol.2019.10341. View

19.

Kerru N, Gummidi L, Maddila S, Gangu K, Jonnalagadda S . A Review on Recent Advances in Nitrogen-Containing Molecules and Their Biological Applications. Molecules. 2020; 25(8). PMC: 7221918. DOI: 10.3390/molecules25081909. View

20.

Mermer A, Keles T, Sirin Y . Recent studies of nitrogen containing heterocyclic compounds as novel antiviral agents: A review. Bioorg Chem. 2021; 114:105076. DOI: 10.1016/j.bioorg.2021.105076. View