SYNTHESIS, STRUCTURAL STUDIES AND ACETYLCHOLINESTERASE INHIBITION ACTIVITY OF SOME (E)-2-METHOXY-3-NITRO-4-(3-OXO-3-ARYLPROP-1-EN-1-YL)PHENYL ACETATES
DOI:
https://doi.org/10.18173/2354-1059.2025-0042Keywords:
vanillin, chalcone, acetate, acetylcholinesteraseAbstract
A semi-synthetic process from vanillin (isolated from vanilla) was developed to obtain new esters with potential inhibitory activity against the acetylcholinesterase (AchE.). 2-Nitrovanillin was synthesized from vanillin by
esterification, nitration, and hydrolysis reactions. Four chalcones were synthesized
by acid-catalyzed condensation reaction of 2-nitrovanillin and methyl aryl ketone. The identity of 2-nitrovanillin and four chalcones was confirmed by thin-layer chromatography compared with the known compounds. Subsequent esterification of the chalcones with acetic anhydride yielded four new derivatives of (E)-2-methoxy-3-nitro-4-(3-oxo-3-(aryl)prop-1-en-1-yl)phenyl acetate. The structures of
the four new compounds were elucidated by 1H NMR and 13C NMR spectra. The
four compounds were evaluated for their inhibitory activity against AChE. and three of them exhibited significant activity.
References
[1] Zhuang C, Zhang W, Sheng C, Zhang W, Xing C, Miao Z, (2017). Chalcone: A Privileged Structure in Medicinal Chemistry. Chemical Reviews, 117(12), 7762–7810. DOI: 10.1021/acs.chemrev.7b00020.
[2] Maria K, Dimitra HL & Maria G, (2008). Synthesis and Anti-Inflammatory Activity of Chalcones and Related Mannich Bases. Medicinal Chemistry, 4, 586-596. DOI: 10.2174/157340608786242070.
[3] Ashok D, Mohan Gandhi D, Srinivas G & Vikas Kumar A, (2014). Microwave-assisted synthesis of novel 1,2,3-triazole derivatives and their antimicrobial activity. Medicinal Chemistry Research, 23, 3005-3018. DOI: 10.1007/s00044-013-0880-1.
[4] Ashok D, Hanumantha Rao V & Sreenivas P, (2013). Microwave-assisted synthesis of 2-(4,5-dihydro-5-(tetrazolo[1,5-a]quinoline-4-yl)-1H-pyrazol-3-yl)-substituted phenols. Heterocyclic Communications, 19(5), 363-367. DOI: 10.1515/hc-2013-0046.
[5] Dhar DN, (1981). The Chemistry of Chalcones and Related Compounds, New York: Wiley.
[6] Bohm BA, Dey PM & Harborne JB, (1989). Chalcones and Aurones: Methods in Plant Biochemistry (Vol. 1), 237-282. DOI: 10.1016/B978-0-12-461011-8.50013-5.
[7] Narender T, Shweta S, Tanvir K, Rao MS, Srivastava K & Puri SK, (2005). Prenylated chalcones isolated from the Crotalaria genus inhibit the in vitro growth of the human malaria parasite Plasmodium falciparum. Bioorganic & Medicinal Chemistry Letters, 15(10), 2453-2455. DOI: 10.1016/j.bmcl.2005.03.081.
[8] Liu M, Wilairat P, Croft SL, Tan AL & Go M, (2003). Structure–Activity Relationships of Antileishmanial and Antimalarial Chalcones. Bioorganic & Medicinal Chemistry, 11(13), 2729-2738. DOI: 10.1016/S0968-0896(03)00233-5.
[9] Lin Y, Zhou Y, Flavin MT, Zhou L, Nie W & Chen F, (2002). Chalcones and Flavonoids as Anti-Tuberculosis Agents. Bioorganic & Medicinal Chemistry, 10(8), 2795-2802. DOI: 10.1016/S0968-0896(02)00094-9.
[10] Rocha S, Ribeiro D, Fernandes E & Freitas M, (2020). A Systematic Review on Anti-diabetic Properties of Chalcones. Current Medicinal Chemistry, 27(14), 2257–2321. DOI: 10.2174/0929867325666181001112226.
[11] Kocyigit UM, Budak Y, Gürdere MB, Ertürk F, Yencilek B, Taslimi P, Gülçin I, Ceylan M, (2018). Synthesis of chalcone-imide derivatives and investigation of their anticancer and antimicrobial activities, carbonic anhydrase and acetylcholinesterase enzymes inhibition profiles. Archives of Physiology and Biochemistry, 124, 61–68. DOI: 10.1080/13813455.2017.1360914.
[12] Karaca H & Kazancı S, (2022). The metal sensing applications of chalcones: The synthesis, characterization, and theoretical calculations. Journal of Molecular Structure, 1248, 131454. DOI: 10.1016/j.molstruc.2021.131454.
[13] Sang Z, Song Q, Cao Z, Deng Y, Zhang L, (2022). Design, synthesis, and evaluation of chalcone–Vitamin E–donepezil hybrids as multi-target-directed ligands for the treatment of Alzheimer’s disease. Journal of Enzyme Inhibition and Medicinal Chemistry, 37(1), 69–85. DOI: 10.1080/14756366.2021.1993845.
[14] George G, Koyiparambath VP, Sukumaran S, Nair AS, Pappachan LK, Al-Sehemi AG, Kim H, Mathew B, (2022). Structural Modifications on Chalcone Framework for Developing a New Class of Cholinesterase Inhibitors. International Journal of Molecular Sciences, 23(6), 3121. DOI: 10.3390/ijms23063121.
[15] Vishal P, Oh J, Khames A, Abdelgawad M, Nair A, Nath L, Gambacorta N, Ciriaco F, Nicolotti O, Kim H, et al. (2021). Trimethoxylated Halogenated Chalcones as Dual Inhibitors of MAO-B and BACE-1 for the Treatment of Neurodegenerative Disorders. Pharmaceutics, 13(6), 850. DOI: 10.3390/pharmaceutics13060850.
[16] Ashok D, Sudershan K & Khalilullah M, (2012). Solvent-free microwave-assisted synthesis of E-(1)-(6-benzoyl-3,5-dimethylfuro[3′,2′:4,5]benzo[b]furan-2-yl)-3-(aryl)-2-propen-1-ones and their antibacterial activity. Green Chemistry Letters and Reviews, 5(2), 121-125. DOI: 10.1080/17518253.2011.584912.
[17] Truong ML & Nguyen THN, (2019). Study on the synthesis and structure of the compounds (E)-1-aryl-3-(4-hydroxy-3-methoxy-2-nitrophenyl)prop-2-en-1-one from vanillin. Vietnam Journal of Chemistry, 57(4e3,4), 35-39 (in Vietnamese).
[18] Tran TD, Tran TS, Nguyen TCV, Le MT & Thai KM, (2017). Synthesis, in vitro acetylcholinesterase inhibitory activity evaluation, and docking investigation of some aromatic chalcones. MedPharmRes, 1(1), 15-25. DOI: 10.32895/UMP.MPR.1.1.15/suffix.
[19] Truong ML, (2017). Synthesis, study of structure and biological activity of some azomethine and hydrazone derivatives of 2-nitrovanillin. Vietnam Journal of Chemistry, 55(5E34), 304-310 (in Vietnamese).
[20] Truong ML & Ngo TL, (2019). Study on synthesis, structure, and biological activity of two new thiazolidine-4-one derivatives from 2-nitrovanillin. HNUE Journal of Science, 64(3), 89-96 (in Vietnamese). DOI: 10.18173/2354-1059.2019-0011.
[21] Truong ML, (2024). Synthesis and structure of some 8-methoxy-2-arylquinolin-7-ol derivatives from vanillin. HNUE Journal of Science, 69(2), 110-117. DOI: 10.18173/2354-1059.2024-0025.
[22] Ellman GL, Courtney KD, Andres V et al, (1961). A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical Pharmacology, 7(2), 88–95. DOI: 10.1016/0006-2952(61)90145-9.
[23] Min BS, To DC, Lee JS et al, (2010). Cholinesterase inhibitors from Cleistocalyx operculatus buds. Archives of Pharmacal Research, 33(10), 1665-1670. DOI: 10.1007/s12272-010-1016-5.
[24] Somani G, Kulkarni C, Shinde P, Shelke R, Laddha K & Sathaye S, (2015). In vitro acetylcholinesterase inhibition by psoralen using molecular docking and enzymatic studies. Journal of Pharmacy and Bioallied Sciences, 7(1), 32–36. DOI: 10.4103/0975-7406.148775.
