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Facile Synthesis, Crystal Structure, DFT Calculation and Biological Activities of 4-(2-fluorophenyl)-3-(3-methoxybenzyl)-1H-1,2,4-triazol-5 (4H)-one (5)

[ Vol. 14 , Issue. 5 ]


Muhammad Saleem, Muhammad Rafiq, Yeon Ki Jeong, Dae Won Cho, Chong-Hyeak Kim, Sung-Yum Seo, Chang-Shik Choi, Seong-Karp Hong and Ki Hwan Lee*   Pages 451 - 459 ( 9 )


Background: In the past few decades, design, synthesis, and characterization of novel heterocyclic compounds with auspicious biological profile received the considerable attention of the scientific community. Among them, the small and simple organic molecular backbone like triazole moiety have a broad spectrum of applications in the medicinal as well as diagnostic areas.

Objective: The objective of present study was synthesis, characterization, and exploration of biological profile of 4-(2-fluorophenyl)-3-(3-methoxybenzyl)-1H-1,2,4-triazole-5(4H)-one (5). The tautomeric interconversion of the molecule was observed by the single crystal XRD and DFT analysis.

Methods: N-(2-fluorophenyl)-2-[2-(3-methoxyphenyl)acetyl]hydrazine carboxamide (4) was synthesized by the condensation of 2-(3-methoxyphenyl)acetohydrazide (3) with 1-fluoro-2- isocyanatobenzene. The dehydrocyclization of compound (4) yielded target compound (5) by refluxing in 2 N aqueous sodium hydroxide solutions. The target molecule was characterized by FTIR, 1H NMR, 13C NMR, single crystal X-ray diffraction analysis and DFT calculation. The enzymatic assay measurements were carried out by using a microplate reader (OPTI Max, Tunable Microplate Reader; Wavelength range: 340-850 nm; for 96-well plates) while DFT calculation was performed by Gaussian 09 package.

Results: The XRD result and DFT calculations showed that molecule 5 predominantly exists in thione conformation and crystallized in the triclinic system of P-1 space group. Furthermore, for the practical applicability of synthesized compound 5, the in vitro acetylcholinesterase as well as α-glucosidase inhibition activities were performed and found moderate enzyme inhibition potential comparable with that of reference inhibitors.

Conclusion: This study might be helpful for future design and development of potent enzyme inhibitor to control Alzheimer's as well as diabetic disease. The DFT and single crystal XRD analysis data might be helpful for understanding the mechanism of drug binding and its mode of action.


Heterocycle, triazole, crystal structure, triclinic, DFT calculation, enzyme inhibition.


Department of Chemistry, University of Sargodha, Sub Campus Mianwali 40100, Department of Biochemistry and Biotechnology (Baghdad-ul-Jadeed Campus), The Islamia University of Bahawalpur, Bahawalpur 63100, Department of Chemistry, Kongju National University, Gongju, Chungnam, 32588, Department of Advanced Materials Chemistry, Korea University, Sejong 30019, Center for Chemical Analysis, Korea Research Institute of Chemical Technology, Yuseong, Daejeon 34114, Department of Biology, Kongju National University, Gongju, Chungnam, 32588, Department of Food and Fermentation, Far East University, Eumseong, Chungbuk 27601, Department of Biomedical Engineering, Mokwon University, Seo-gu, Daejeon, 35349, Department of Chemistry, Kongju National University, Gongju, Chungnam, 32588

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