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Letters in Drug Design & Discovery

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ISSN (Print): 1570-1808
ISSN (Online): 1875-628X

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Research Article

Synthesis and Evaluation of Chalcone and its Derivatives as Potential Anticholinergic Agents

Author(s): Shahzad Murtaza*, Khoula Zubair Mir, Adina Tatheer and Raja Summe Ullah

Volume 16, Issue 3, 2019

Page: [322 - 332] Pages: 11

DOI: 10.2174/1570180815666180523085436

Price: $65

Abstract

Background: Structural similarity in Chalcone and Pyrazoline brought our intention for the analysis of such compounds. This study involved the synthesis of chalcones and their pyrazoline derivatives and their screening as cholinesterase inhibitors. The newly synthesized compounds were also investigated for their antioxidant potential.

Methods: Chalcones were synthesized by well-established methods of synthesis and their structural elucidation was carried out by H-NMR, 13C-NMR, Mass spectrometry and FTIR. For the determination of inhibition potency of synthesized compounds, spectrophotometric method was applied whereas, DPPH free radical scavenging method was used to check the antioxidant ability.

Results: Chalcones and their pyrazoline derivatives were synthesized and characterised by 1HNMR, 13C-NMR, Mass spectrometry and FTIR. The compounds were screened for their anti- Alzheimer activity, which exhibited that compounds 1g, 1c and 1h, 1g showed strong inhibitory potency against acetylcholinesterase and butyrylcholinesterase, respectively. DPPH radical scavenging method was applied to check anti-oxidant potential of synthesized compounds and results explored that among all the synthesized compounds only compounds 1c and 1b showed strong scavenging potential.

Conclusion: Chalcone and their pyrazoline derivatives were synthesized and screened for their anti-Alzheimer and antioxidant potential. The experimental results of anti-Alzheimer activity were compared with molecular docking studies, which showed that compounds 1g, 1c and 1h, 1g were active against AChE and BChE, respectively. Among the synthesized compounds 1c and 1b were found to be most potent antioxidants. These results suggest that compound 1b, 1c, 1g and 1h may further be explored for further developments.

Keywords: Antioxidant, chalcone, cholinesterase inhibition, molecular docking, pyrazoline, structure activity relationship.

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[1]
Rao, A.A.; Sridhar, G.R.; Das, U.N. Elevated butyrylcholinesterase and acetylcholinesterase may predict the development of type 2 diabetes mellitus and Alzheimer’s disease. Med. Hypotheses, 2007, 69, 1272-1276.
[2]
Kaplay, S.S. Acetylcholinesterase and butyrylcholinesterase of developing human brain. Biol. Neonate, 1976, 28, 65-73.
[3]
Geula, C.; Mesulam, M.M. Cholinesterases and the pathology of Alzheimer disease. Alzheimer Dis. Assoc. Disord., 1995, 9, 23-28.
[4]
Shaik, J.B.; Palaka, B.K.; Penumala, M.; Kotapati, K.V.; Devineni, S.R.; Eadlapalli, S.; Darla, M.M.; Ampasala, D.R.; Vadde, R.; Amooru, G.D. Synthesis, pharmacological assessment, molecular modeling and in silico studies of fused tricyclic coumarin derivatives as a new family of multifunctional anti-Alzheimer agents. Eur. J. Med. Chem., 2016, 107, 219-232.
[5]
Tarazi, H.; Odeh, R.A.; Al-Qawasmeh, R.; Yousef, I.A.; Voelter, W.; Al-Tel, T.H. Design, synthesis and SAR analysis of potent BACE1 inhibitors: Possible lead drug candidates for Alzheimer’s disease. Eur. J. Med. Chem., 2016, 125, 1213-1224.
[6]
Thathiah, A.; De-Strooper, B. The role of G protein-coupled receptors in the pathology of Alzheimer’s disease. Nat. Rev. Neurosci., 2011, 12, 73-87.
[7]
Zhao, L.M.; Jin, H.S.; Sun, L.P.; Piao, H.R.; Quan, Z.S. Synthesis and evaluation of antiplatelet activity of trihydroxychalcone derivatives. Bioorg. Med. Chem. Lett., 2005, 15, 5027-5029.
[8]
Abdel-Aziz, M.; Abuo-Rahma, G.A.; Hassan, A.A. Synthesis of novel pyrazole derivatives and evaluation of their antidepressant and anticonvulsant activities. Eur. J. Med. Chem., 2009, 44, 3480-3487.
[9]
Pande, P.S.; Khan, S.H.; Malpani, M.O. Evaluation of qualitative and quantitative antioxidant activity of some pyrazolines. World J. Pharm. Sci., 2017, 6(3), 1085-1089.
[10]
Dipankar, B.; Panneerselvam, P.; Asish, B. Synthesis, characterization and evaluation of analgesic, anti-inflammatory, ulcerogenic potential of some 2-pyrazoline derivatives. Der. Pharma. Chemica., 2012, 4, 1679-1688.
[11]
Jadhav, S.B.; Rathod, S.D. Synthesis of Some Novel 3, 5-Diaryl-N-chalcone-2-pyrazoline Derivatives and Evaluation of their Antimicrobial Activity. Chem. Sci. Trans., 2016, 5, 109-116.
[12]
EI-Sabbagh, O. I.; Baraka, M.M.; Ibrahim, S.M.; Pannecouque, C.; Andrei, G.; Snoeck, R.; Balzarini, J.; Rashad A.A. Synthesis and antiviral activity of new pyrazole and thiazole derivatives. Eur. J. Med. Chem., 2009, 44, 3746-3753.
[13]
Abdel-Wahab, B.F.; Abdel-Aziz, H.A.; Ahmed, E.M. Synthesis and antimicrobial evaluation of 1-(benzofuran-2-yl)-4-nitro-3-arylbutan-1-ones and 3-(benzofuran-2-yl)-4,5-dihydro-5-aryl-1-[4-(aryl)-1,3-thiazol-2-yl]-1H-pyrazoles. Eur. J. Med. Chem., 2009, 44, 2632-2635.
[14]
Solankee, A.; Tailor, R. Synthesis, Characterisation and Biological Screening of s-Triazine Based Chalcones and its Derivatization into Phenyl Pyrazolines, Isoxazoles. ILCPA, 2015, 47, 109-119.
[15]
Salum, L.B.; Altei, W.F.; Chiaradia, L.D.; Cordeiro, M.N.S.; Canevarolo, R.R.; Melo, C.P.; Winter, E.; Mattei, B.; Daghestani, H.N.; Santos-Silva, M.C.; Creczynski-Pasa, T.B.; Yunes, R.A.; Yunes, J.A.; Andricopulo, A.D.; Day, B.W.; Nunes, R.J.; Vogt, A. Cytotoxic 3,4,5-trimethoxychalcones as mitotic arresters and cell migration inhibitors. Eur. J. Med. Chem., 2013, 63, 501-510.
[16]
Gupta, R.A.; Kaskhedikar, S.G. Synthesis, antitubercular activity, and QSAR analysis of substituted nitroaryl analogs: Chalcone, pyrazole, isoxazole, and pyrimidines. Med. Chem. Res., 2013, 22, 3863-3880.
[17]
Tomar, V.; Bhattacharjee, G. Kamaluddin; Rajakumar, S.; Srivastava, K.; Puri, S.K. Synthesis of new chalcone derivatives containing acridinyl moiety with potential antimalarial activity. Eur. J. Med. Chem., 2010, 45, 745-751.
[18]
Rizvi, S.U.F.; Siddiqui, H.L.; Johns, M.; Detorio, M.; Schinazi, R.F. Anti-HIV-1 and cytotoxicity studies of piperidyl-thienyl chalcones and their 2-pyrazoline derivatives. Med. Chem. Res., 2012, 21, 3741-3749.
[19]
Tripathi, A.; Srivastava, U.C. Acetylcholinesterase: A versatile enzyme of nervous system. Ann. Neurosci., 2008, 15, 106-111.
[20]
Masson, P.; Carletti, E.; Nachon, F. Structure, Activities and Biomedical Applications of Human Butyrylcholinesterase. Protein Pept. Lett., 2009, 16, 1215-1224.
[21]
Sussman, J.L.; Harel, M.; Frolow, F.; Oefner, C.; Goldman, A.; Toker, L.; Silman, I. Atomic structure of acetylcholinesterase from Torpedo californica: A prototypic acetylcholine-binding protein. Science, 1991, 253, 872-879.
[22]
Christen, Y. Oxidative stress and Alzheimer disease. Am. J. Clin. Nutr., 2000, 71, 621S-629S.
[23]
Dong, F.; Jian, C.; Zhenghao, F.; Kai, G.; Zuliang, L. Synthesis of biologically active chalcon analogues via claisen-schmidt condensation in solvent-free conditions: Supported mixed addenda heteropoly acid as a heterogeneous catalyst. Catal. Commun., 2008, 9, 1924-1927.
[24]
Murtaza, S.; Abbas, A.; Iftikhar, K.; Shamim, S.; Akhtar, M.S.; Razzaq, Z.; Naseem, K.; Elgorban, A.M. Synthesis, biological activities and docking studies of novel 2,4-dihydroxybenzaldehyde based Schiff base. Med. Chem. Res., 2016, 25, 2860-2871.
[25]
Batovska, D.; Parushev, S.; Stamboliyska, B.; Tsvetkova, I.; Ninova, M.; Najdenski, H. Examination of growth inhibitory properties of synthetic chalcones for which antibacterial activity was predicted. Eur. J. Med. Chem., 2009, 44, 2211-2218.
[26]
Ellman, G.L.; Courtney, K.D.; Andres, Jr , V.; Featherstone, R.M. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem. Pharmacol., 1961, 7, 88-90.
[27]
Abbas, A.; Murtaza, S.; Tahir, M.N.; Shamim, S.; Sirajuddin, M.; Rana, U.A.; Naseem, K.; Rafique, H. Synthesis, antioxidant, enzyme inhibition and DNA binding studies of novel N-benzylated derivatives of sulfonamide. J. Mol. Struct., 2016, 1117, 269-275.
[28]
Murtaza, S.; Akhtar, M.S.; Kanwal, F.; Abbas, A.; Ashiq, S.; Shamim, S. Synthesis and biological evaluation of schiff bases of 4-aminophenazone as an anti-inflammatory, analgesic and antipyretic agent. J. Saudi Chem. Soc., 2017, 21, S359-S372.
[29]
Nachon, F.; Carletti, E.; Ronco, C.; Trovaslet, M.; Nicolet, Y.; Jean, L.; Renard, P.Y. Crystal structures of human cholinesterases in complex with huprine W and tacrine: elements of specificity for anti-Alzheimer’s drugs targeting acetyl- and butyryl-cholinesterase. Biochem. J., 2013, 453, 393-399.
[30]
ACD/ChemSketch, in Advanced Chemistry Development, Inc., Toronto, On, Canada, 2015.
[31]
D.S., Visualizer Accelrys software inc; Discovery Studio Visualizer, 2005, p. 2.
[32]
Murtaza, S.; Akhtar, M.S.; Kanwal, F.; Abbas, A.; Ashiq, S.; Shamim, S. Synthesis and biological evaluation of schiff bases of 4-aminophenazone as an anti-inflammatory, analgesic and antipyretic agent. J. Saudi Chem. Soc., 2017, 21, S359-S372.

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