• Eatedal H Abd El-aal Zagazig University
  • Hanan A Abdel Fattah Zagazig University
  • Nermine A Osman Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Zagazig University, Zagazig, 44519, Egypt
  • Israa A Seliem Zagazig University


Objectives: The objective of this work is to synthesize novel imidazole and fused imidazole derivatives using 5-arylidene-2-hydrazino-3-phenyl imidazolin-4-ones (5a-c) as key intermediate. The structure of the newly synthesized compounds was characterized using IR, 1HNMR, Mass spectroscopy, elemental analysis and some representative 13CNMR.

Methods: The target compounds were synthesized starting from 5-arylidene-2-hydrazino-3-phenyl imidazolin-4-ones (5a-c) which prepared from the appropriate 5-arylidene-2-(methylthio)-3-phenyl imidazolin-4-ones (3a-c). Several synthetic pathways were be used for the preparation of the targets. Some of the newly synthesized compounds were evaluated for their cytotoxic activity against breast carcinoma and colon carcinoma cell lines. On the other hand, the antimicrobial activity evaluation of some newly prepared compounds was performed using cup plate diffusion method.

Results: Compound 5c was the most active one against breast carcinoma (IC50=3.3 ug/ml) and colon carcinoma cell lines (IC50=4.73 ug/ml) when compared with doxorubicin as standard. Molecular docking studies further supported the highest potency of 5c and further help understanding the various interactions between the ligand and enzyme active sites. On the other hand, the antimicrobial activity evaluation showed that most of the evaluated compounds exhibited broad spectrum activity.

Conclusion: The present work led to the development of promising antitumor compounds containing substituted imidazolidin-5-one or imidazotriazol-6-one skeletons. Compounds 5c showed the highest potency at low µg/ml level against breast MCF-7 and colon HCT116 cell lines. On the other hand, most of the newly synthesized compounds showed broad spectrum antimicrobial activity when cup plate diffusion method was performed.


Keywords: Imidazole, Fused imidazole derivatives, Cytotoxic, Antimicrobial activity


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1. Zhang L, Peng XM, Damu GLV, Geng RX, Zhou CH. Comprehensive review in current developments of imidazole-based medicinal chemistry. Med Res Rev 2014;34:340-437.
2. Yurttaş L, Duran M, Demirayak Ş, Gençer HK, Tunalı Y. Synthesis and initial biological evaluation of substituted 1-phenylamino-2-thio-4,5-dimethyl-1H-imidazole derivatives. Bioorg Med Chem Lett 2013;23:6764-8.
3. Assadieskandar A, Amirhamzeh A, Salehi M, Ozadali K, Ostad SN, Shafiee A, et al. Synthesis, cyclooxygenase inhibitory effects, and molecular modeling study of 4-aryl-5-(4-(methylsulfonyl)phenyl)-2-alkylthio and-2-alkylsulfonyl-1H-imidazole derivatives. Bioorg Med Chem 2013;21:2355–62.
4. Bhatnagar A, Sharma PK, Kumar N. A review on imidazoles: Their chemistry and pharmacological potentials. Int J Pharm Tech Res 2011;3:268-82.
5. Bellina F, Cauteruccio S, Rossi R. Synthesis and biological activity of vicinal diaryl-substituted 1-imidazoles. Tetrahedron 2007;63:4571-624.
6. Weitman M, Nudelman A. Carboxamido-substituted imidazoles from 1,2,3-tricarbonyl derivatives and acetamido-substituted thiazoles from 4-bromo-3-oxo-butanenitriles. ARKIVOC J 2008;16:119-29.
7. Brogden RN, Heel RC, Speight TM, Avery GS. Metronidazole in Anaerobic Infections: a review of its activity, Pharmacokinetics and therapeutic use. Drugs 1978;16:387-417.
8. Sadek B. Imidazole-substituted drugs and tendency for inhibition of Cytochrome P450 isoenzymes: a review. Pharm Chem 2011;3:410-9.
9. Jones GL, Wimbish GH, McIntosh WE. Phenytoin: basic and clinical pharmacology. Med Res Rev 1983;3:383-434.
10. Flouret G. Synthesis of pyroglutamylhistidylprolineamide by classical and solid phase methods. J Med Chem 1970;13:843-5.
11. Cooper DS. Antithyroid Drugs. N Engl J Med 1984;311:1353-62.
12. Mayorga AJ, Cousins MS, Trevitt JT, Coulan A, Gianutsos G, Salamone JD. Characterization of the muscarinic receptor subtype mediating pilocarpine-induced tremulous jaw movements in rats. Eur J Pharmacol 1999;364:7-11.
13. Godefroi EF, Janssen PAJ, Van der Eycken CAM, Vanheertum AHMT, Niemegeers CJE. DL-1-(1-Arylalkyl)imidazole-5-carboxylate esters. A novel type of hypnotic agents. J Med Chem 1965;8:220-3.
14. Abu Al-Nasr AK. Mercury (II) and Silver (I) complexes of 3-phenyl-2-thiohydantoin. J King Abdulaziz University Sci 2000;12:85-90.
15. Khalifa MA, Hassaan AMA. Synthesis and structural study on new complexes of dioxouranium 9V10 with some 2-thiohydantoin derivatives. Sulfur Lett 1994;17:261.
16. Maged El-Din AA, Roaiah HF, Elsharabasy SA, Hassan AY. A novel synthesis of some new imidazothiazole and glycocyamidine derivatives and studies on their antimicrobial activities. Phosphorus Sulfur Silicon Relat Elem 2007;182:529-36.
17. Khodair AI. A Convenient preparation of 2-(2-Arylidene)-and 2-(2-Polyhydroxyalkylidene) hydrazono-4-imidazolidinones with various heterocyclic side chain substituents at position 5 as potential antiviral and antitumor agents. Phosphorus Sulfur Silicon Relat Elem 2002;177:1157-73.
18. Skehan P, Storeng R, Scudiero D, Monks A, McMahon J, Vistica D, et al. New colorimetric cytotoxicity assay for anticancer-drug screening. J Natl Cancer Inst 1990;82:1107-12.
19. William H. "Microbiological assay, An introduction to quantitative principles and evaluation", Academic press, New York; 1977. p. 1-68.
20. Kwon-Chung KJ, Bennett JE. "Medical Mycology", Lea and Febiger, Philadelphia-London; 1992. p. 81-102.
21. Al-Tamamy HA, Abdel Fattah ME. Synthesis and antibacterial activity of some new imidazole, Imidazo[2,1-c]triazole and Imidazo[1,2-e]tetrazole derivatives. Orient J Chem 2010;26:421-7.
22. Al-Ashmawy MI, Abd El-Samii ZK, El-Feky SA, Osman NA. Utility of 2-hydrazino-4,6-dimethylpyrimidine in heterocyclic synthesis. Zagazig J Pharm Sci 1997;6:1-6.
23. Shalaby AFA, Daboun HA, Abdel Aziz MA. Novel rearrangement of 5-arylazo-2-thiohydantoin derivatives with alkali and aromatic amines. Z Naturforsch 1978;33b:937-41.
24. Shirai H, Yashiro T. Studies on the synthesis and antibacterial activity of thiohydantion related compounds. Yakugaku Zasshi 1967;87:137-42.
25. Kadry AM, Abdelal EH, Abdel Fattah HA. Synthesis of some new imidazolinones of expected antimicrobial activity. Bull Fac Pharm Cairo Univ 1991;29:21-5.
26. Alanazi AM, El-Azab AS, Al-Swidan IA, Maaruf AR, El-Bendary ER, Abu El-Enin MA, et al. Synthesis, single-crystal, in vitro antitumor evaluation and molecular docking of 3-substitued 5,5-diphenylimidazolidine-2,4-dione derivatives. Med Chem Res 2013;22:6129–42.
27. Barry AL. The antimicrobial susceptibility test: Principle and practices, edited by Illus, Lea & Febiger, (Philadelphia), USA, 180. Biol Abstr 1977;64:25183.
28. National Committee for clinical laboratory standards (NCCLS) Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard M100-512. Wayne. PA, NCCES; 2002.
29. Gaydos JM, Harrington BJ. Agar disk diffusion for the quality control testing of Autobac elution disks. 1982;21:516–8.
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How to Cite
El-aal, E. H. A., H. A. A. Fattah, N. A. Osman, and I. A. Seliem. “SYNTHESIS OF NOVEL IMIDAZOLE AND FUSED IMIDAZOLE DERIVATIVES AS CYTOTOXIC AND ANTIMICROBIAL AGENTS: MOLECULAR DOCKING AND BIOLOGICAL EVALUATION”. International Journal of Pharmacy and Pharmaceutical Sciences, Vol. 7, no. 11, Aug. 2015, pp. 36-45,
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