Pyridine and Benzoisothiazole Decorated Vanillin Chalcones: Synthesis, Antimicrobial, Antioxidant, Molecular Docking Study and ADMET Properties

Author(s): Pintu Pathare, Sunil Tekale, Rafique Shaikh, Manoj Damale, Jaiprakash Sangshetti, Dhanaji Rajani, Rajendra Pawar*

Journal Name: Current Organic Synthesis

Volume 17 , Issue 5 , 2020

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Graphical Abstract:


Background: The search for new antimicrobial drugs is a never-ending task due to microbial resistance to the existing drugs. Antioxidants are essential to prevent free radical reactions which lead to chronic diseases to humankind.

Objective: The present studies were aimed at synthesis, characterization, antimicrobial and antioxidant activities of pyridine and benzoisothiazole decorated chalcones.

Materials and Methods: FTIR spectra were recorded using KBr pellets on Shimadzu FT-IR spectrophotometer. 1H and 13C NMR spectra were recorded on Bruker 400 MHz spectrometer. Antimicrobial activity of the synthesized chalcones was found to be good against different bacterial and fungal strains. Antioxidant activity was studied in terms of 2,2-diphenyl-1-picrylhydrazyl, hydroxyI and superoxide radical scavenging activities. Molecular docking was studied using Discovery Studio Visualizer Software, version 16 whereas Autodock Vina program was used to predict the toxicity profile of the compounds using FAFDrugs2 predictor.

Results and Discussion: The compounds 5c, 5d & 6c showed good antioxidant activities. The insilico molecular docking study supports the experimental results and demonstrated that the chalcones 5d, 6a and 7a are the most active among the synthesized derivatives.

Conclusion: Prediction of pharmacokinetic parameters and molecular docking studies suggest that the synthesized chalcones have good pharmacokinetic properties to act as lead molecules in the drug discovery process.

Keywords: Benzoisothiazole, pyridine, chalcones, antimicrobial, antioxidant, molecular docking, ADMET.

Kerler, J.; Verpoorte, R. Vanilla production: Technological, chemical, and biosynthetic aspects. Food Rev. Int., 2001, 17(2), 119-120. Available at
Ravendra, K.; Sharma, P.K.; Mishra, P.S. A review on the vanillin derivatives showing various biological activities. Int. J. Pharm. Tech. Res., 2012, 4(1), 266-279.
Sinha, A.K.; Sharma, U.K.; Sharma, N. A comprehensive review on vanilla flavor: extraction, isolation and quantification of vanillin and others constituents. Int. J. Food Sci. Nutr., 2008, 59(4), 299-326.
[] [PMID: 17886091]
Marin, L.; Stoica, I.; Mares, M.; Dinu, V.; Simionescu, B.C.; Barboiu, M. Antifungal vanillin-imino-chitosan biodynameric films. J. Mater. Chem. B Mater. Biol. Med., 2013, 1(27), 3353-3358.
Lirdprapamongkol, K.; Sakurai, H.; Kawasaki, N.; Choo, M.K.; Saitoh, Y.; Aozuka, Y.; Singhirunnusorn, P.; Ruchirawat, S.; Svasti, J.; Saiki, I. Vanillin suppresses in vitro invasion and in vivo metastasis of mouse breast cancer cells. Eur. J. Pharm. Sci., 2005, 25(1), 57-65.
[] [PMID: 15854801]
Nabi, G.; Liu, Z.Q. Radical-scavenging properties of ferrocenyl chalcones. Bioorg. Med. Chem. Lett., 2011, 21(3), 944-946.
[] [PMID: 21215630]
Baluja, S.; Vakariya, N.; Hirapara, A. Synthesis and physicochemical studies of vanillin chalcones. Revista Colombiana de Ciencias Químico-Farmacéuticas, 2018, 47(2), 185-215.
Patel, N.B.; Patel, N.B.; Patel, H.R. Synthesis and pharmacological studies of 5-ethyl pyridin-2-ethanol analogs derivatives. ARKIVOC, 2009, xii, 302-321.
Prashar, H.; Chawla, A.; Sharma, A.K.; Kharb, R. Chalcone as a versatile moiety for diverse pharmacological activities. IJPSR, 2012, 3(7), 1913-1927.
Prasad, Y.R.; Rao, A.L.; Rambabu, R. Synthesis and antimicrobial activity of some chalcone derivatives. E-J. Chem., 2008, 5(3), 461-466.
Nowakowska, Z. A review of anti-infective and anti-inflammatory chalcones. Eur. J. Med. Chem., 2007, 42(2), 125-137.
[] [PMID: 17112640]
Won, S.J.; Liu, C.T.; Tsao, L.T.; Weng, J.R.; Ko, H.H.; Wang, J.P.; Lin, C.N. Synthetic chalcones as potential anti-inflammatory and cancer chemopreventive agents. Eur. J. Med. Chem., 2005, 40(1), 103-112.
[] [PMID: 15642415]
Anto, R.J.; Sukumaran, K.; Kuttan, G.; Rao, M.N.A.; Subbaraju, V.; Kuttan, R. Anticancer and antioxidant activity of synthetic chalcones and related compounds. Cancer Lett., 1995, 97(1), 33-37.
[] [PMID: 7585475]
Ahmad, A.L.M.; Dowsett, A.B.; Tyrrell, D.A.J. Studies of rhinovirus resistant to an antiviral chalcone. Antiviral Res., 1987, 8(1), 27-39.
[] [PMID: 2825590]
Ahmad, I.; Thakur, J.P.; Chanda, D.; Saikia, D.; Khan, F.; Dixit, S.; Kumar, A.; Konwar, R.; Negi, A.S.; Gupta, A. Syntheses of lipophilic chalcones and their conformationally restricted analogues as antitubercular agents. Bioorg. Med. Chem. Lett., 2013, 23(5), 1322-1325.
[] [PMID: 23369537]
Rohrmann, E.; Jones, R.G.; Shonle, H.A. The use of chalcones in the synthesis of medicinal intermediates. J. Am. Chem. Soc., 1944, 66(11), 1856-1857.
Yun, J.M.; Kweon, M; Hwang, H; Mukhtar, H. Induction of apoptosis and cell cycle arrest by a chalcone panduratin A isolated from Kaempferia pandurata in androgen-independent human prostate cancer cells PC3 and DU145. Carcinogenesis, 2006, 27(7), 1454-1464.
Sashidhara, K.V.; Kumar, A.; Kumar, M.; Sarkar, J.; Sinha, S. Synthesis and in vitro evaluation of novel coumarin-chalcone hybrids as potential anticancer agents. Bioorg. Med. Chem. Lett., 2010, 20(24), 7205-7211.
[] [PMID: 21071221]
Tatsuzaki, J.; Bastow, K.F.; Nakagawa-Goto, K.; Nakamura, S.; Itokawa, H.; Lee, K.H. Dehydrozingerone, chalcone, and isoeugenol analogues as in vitro anticancer agents. J. Nat. Prod., 2006, 69(10), 1445-1449.
[] [PMID: 17067159]
Ngameni, B.; Kuete, V.; Ambassa, P.; Justin, K.; Marlyse, M.L.; Tehoukoua, A.; Roy, R.; Ngadjui, T.; Tetsuya, M. Synthesis and evaluation of anticancer activity of O-allyl chalcone derivatives. Med. Chem., 2013, 3(3), 233-237. 10.4172/2161-0444.1000144
Prasad, Y.R.; Kumar, P.P.; Kumar, P.R.; Rao, A.S. Synthesis and antimicrobial activity of some new chalcones of 2-acetyl pyridine. J. Chem., 2008, 5(1), 144-148.
Yoo, E.; Hayat, F.; Rhim, H.; Park Choo, H.Y. Synthesis and biological evaluation of benzoisothiazole derivatives possessing N,N dimethylformimidamide group as 5-HT6 receptor antagonists. Bioorg. Med. Chem., 2012, 20(8), 2707-2712.
[] [PMID: 22405919]
Hassan, A.Y.; Sarg, M.T.E.M. Hussein design, synthesis, and anticancer activity of novel benzothiazole analogues J. Het. Chem., 2019, 56(4), 1437-1457.
Trott, O.; Olson, A.J. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comput. Chem., 2010, 31, 455-461.
Nielsen, S.F.; Larsen, M.; Boesen, T.; Schonning, K.; Kromann, H. Cationic chalcone antibiotics. Design, synthesis, and mechanism of action. J. Med. Chem., 2005, 48, 2667-2677.
Sánchez-Moreno, C.; Larrauri, J.A.; & Saura-Calixto, F. A procedure to measure the antiradical efficiency of polyphenols. J. Sci. Food & Agri., 1998, 76(2), 270-276.
Rollet-Labelle, E.; Gragne, M.S.; Elbim, C.; Marquetty, C.; Gougerot-Pocidalo, M.A. Free Rad Hydroxyl radical as a potential intracellular mediator of polymorphonuclear neutrophil apoptosis. Biol. Med., 1998, 24, 563-572.
Liu, F.; Ooi, V.E.C.; Chang, S.T. Free radical scavenging activities of mushroom polysaccharide extracts. Life Sci., 1997, 60, 763-771.
Carlo, C. M.; Ana, A.; Esther, C.; Woon, Y.; Astrid, Z. ; Steven, I.; Alexandre, M.; Olivier, V.; Anna, M. R.; Viviana, J. ; André, L.; Bernard, J.; Christopher, J.S.; Andréa, D. Structure-guided design of cell wall biosynthesis inhibitors that overcome β-lactam resistance in staphylococcus aureus (MRSA). ACS Chem. Biol., 2011, 6(9), 943-951.
Decuyper, L.; Deketelaere, S.; Vanparys, L.; Jukič, M.; Sosič, I.; Sauvage, E.; Amoroso, A.M.; Verlaine, O.; Joris, B.; Gobec, S. In silico design and enantioselective synthesis of functionalized monocyclic 3-amino-1-carboxymethyl-β-lactams as inhibitors of penicillin‐binding proteins of resistant bacteria. PBP1B. Chem, 2018, 24(57), 15254-15266.
Kauthale, S.; Tekale, S.; Damale, M.; Sangshetti, J.; Pawar, P. Synthesis, antioxidant, antifungal, molecular docking and ADMET studies of some thiazolyl hydrazones. Bioorg. Med. Chem. Lett., 2017, 27, 3891-3896.
Deshmukh, S.U.; Kharat, K.R.; Yadav, A.R.; Shisodia, S.U.; Damale, M.G.; Sangshetti, J.N.; Pawar, R.P. Synthesis of novel alpha-aminophosphonate derivatives, biological evaluation as potent antiproliferative agents and molecular docking. ChemistrySelect, 2018, 3(20), 5552-5558.
Sangshetti, J.N.; Khan, F.A.K.; Chouthe, R.S.; Damale, M.G.; Shinde, D.B. Synthesis, docking and ADMET prediction of novel 5-((5-substituted-1-H-1, 2, 4-triazol-3-yl) methyl)-4, 5, 6, 7-tetrahydrothieno [3, 2-c] pyridine as antifungal agents. Chin. Chem. Lett., 2014, 25(7), 1033-1038.
Lagorce, D.; Sperandio, O.; Galons, H.; Miteva, M.A.; Villoutreix, B.O. FAF-Drugs2: free ADME/tox filtering tool to assist drug discovery and chemical biology projects. BMC Bioinformatics, 2008, 9, 396.
Lipinski, C.A.; Lombardo, F.; Dominy, B.W.; Feeney, P.J. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev., 2001, 46(1-3), 3-26.

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Article Details

Year: 2020
Published on: 27 July, 2020
Page: [367 - 381]
Pages: 15
DOI: 10.2174/1570179417666200407130122
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