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Current Chemical Biology

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ISSN (Print): 2212-7968
ISSN (Online): 1872-3136

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Research Article

POCl3 Mediated Syntheses, Pharmacological Evaluation and Molecular Docking Studies of Some Novel Benzofused Thiazole Derivatives as a Potential Antioxidant and Anti-inflammatory Agents

Author(s): Dattatraya G. Raut*, Sandeep B. Patil, Prafulla B. Choudhari, Vikas D. Kadu, Anjana S. Lawand, Mahesh G. Hublikar and Raghunath B. Bhosale

Volume 14, Issue 1, 2020

Page: [58 - 68] Pages: 11

DOI: 10.2174/2212796813666191118100520

Abstract

Background: The present research work is focused on the development of alternative antioxidant and anti-inflammatory agents. The review of the literature reveals that many benzofused thiazole analogues have been used as lead molecules for the design and development of therapeutic agent, including anticancer, anti-inflammatory, antioxidant and antiviral. The synthesized benzofused thiazole derivatives are evaluated for in vitro antioxidant, anti-inflammatory activities and molecular docking study. Thus, the present research work aims to synthesize benzofused thiazole derivatives and to test their antioxidant and antiinflammatory activities.

Objective: To design and synthesize an alternative antioxidant and anti-inflammatory agents.

Methods: The substituted benzofused thiazoles 3a-g were prepared by cyclocondensation reaction of appropriate carboxylic acid with 2-aminothiophenol in POCl3 and heated for about 2-3 h to offer benzofused thiazole derivatives 3a-g. All the newly synthesized compounds were in vitro screened for their anti-inflammatory and antioxidant activities by using a known literature method.

Results: At the outset, the study of in vitro indicated that the compounds code 3c, 3d and 3e possessed distinct anti-inflammatory activity as compared to a standard reference. All the tested compounds show potential antioxidant activity against one or more reactive (H2O2, DPPH, SO and NO) radical scavenging species. Additionally, docking simulation is further performed to the position of compounds 3d & 3e into the anti-inflammatory active site to determine the probable binding model.

Conclusion: New anti-inflammatory and antioxidant agents were needed; it has been proved that benzofused thiazole derivatives were 3c, 3d and 3e constituted as an interesting template for the evaluation of new anti-inflammatory agents and an antioxidant’s work also may provide an interesting template for further development.

Keywords: POCl3, benzofused thiazoles, antioxidant activity, anti-inflammatory activity, pharmacokinetic study, molecular modeling.

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[1]
Kini S, Swain S. Synthesis and evaluation of novel benzothiazole derivatives against human cervical cancer cell lines. Indian J Pharm Sci 2007; 69(1): 46-50.
[http://dx.doi.org/10.4103/0250-474X.32107]
[2]
Wang M, Gao M, Mock BH, et al. Synthesis of carbon-11 labeled fluorinated 2-arylbenzothiazoles as novel potential PET cancer imaging agents. Bioorg Med Chem 2006; 14(24): 8599-607.
[http://dx.doi.org/10.1016/j.bmc.2006.08.026] [PMID: 16962783]
[3]
Raut DG, Patil SB, Kadu VD, Bhosale RB. Synthesis of asymmetric 1-thiocarbamoyl pyrazoles as potent anti-colon cancer, antioxidant and anti-inflammatory agent. Anticancer Agents Med Chem 2018; 18(15): 2117-23.
[http://dx.doi.org/10.2174/1871520618666181112122528] [PMID: 30417799]
[4]
Hutchinson I, Chua MS, Browne HL, et al. Antitumor benzothiazoles. 14. Synthesis and in vitro biological properties of fluorinated 2-(4-aminophenyl)benzothiazoles. J Med Chem 2001; 44(9): 1446-55.
[http://dx.doi.org/10.1021/jm001104n] [PMID: 11311068]
[5]
Trapani V, Patel V, Leong CO, et al. DNA damage and cell cycle arrest induced by 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203, NSC 703786) is attenuated in aryl hydrocarbon receptor deficient MCF-7 cells. Br J Cancer 2003; 88(4): 599-605.
[http://dx.doi.org/10.1038/sj.bjc.6600722] [PMID: 12592376]
[6]
Kok SH, Gambari R, Chui CH, et al. Synthesis and anti-cancer activity of benzothiazole containing phthalimide on human carcinoma cell lines. Bioorg Med Chem 2008; 16(7): 3626-31.
[http://dx.doi.org/10.1016/j.bmc.2008.02.005] [PMID: 18295491]
[7]
Kashiyama E, Hutchinson I. Synthesis, metabolic formation, and biological properties of the C- and N-oxidation products of antitumour 2-(4-aminophenyl) benzothiazoles. J Med Chem 1999; 42: 4172-84.
[http://dx.doi.org/10.1021/jm990104o] [PMID: 10514287]
[8]
Sreenivasa M, Jaychand E. Synthesis of bioactive molecule flurobenzothiazole comprising potent heterocylic moieties for anthelmintic activity. J Arch Pharm Sci and Res 2009; 1(2): 150-7.Avaialble from: . http://www.apsronline.com/Archives%20APSR/Documents/October%202009/01022009008.pdf
[9]
Balaji PN, Ranganayakulu D. Anthelmintic and anti-microbial activities of synthesized heterocyclic pyrazole and its derivatives from fluoro substituted hydrazino benzothiazole. Int J Pharm Tech Res 2014; 6(7): 1970-5.Avaialble From:. https://www.ejbps.com/ejbps/abstract_id/463
[10]
Meltzer-Mats E, Babai-Shani G, Pasternak L, et al. Synthesis and mechanism of hypoglycemic activity of benzothiazole derivatives. J Med Chem 2013; 56(13): 5335-50.
[http://dx.doi.org/10.1021/jm4001488] [PMID: 23750537]
[11]
Pattan S, Suresh C. Synthesis and antidiabetic activity of 2-amino[5′(4-sulphonylbenzylidine)-2,4- thiazolidinedione]-7-chloro-6-fluorobenzothiazole. Indian J Chem 2005; 44B:: 2404-8.Available From:. http://hdl.handle.net/123456789/9231
[12]
Vu CB, Milne JC, Carney DP, et al. Discovery of benzothiazole derivatives as efficacious and enterocyte-specific MTP inhibitors. Bioorg Med Chem Lett 2009; 19(5): 1416-20.
[http://dx.doi.org/10.1016/j.bmcl.2009.01.044] [PMID: 19181526]
[13]
Aiello S, Wells G, Stone EL, et al. Synthesis and biological properties of benzothiazole, benzoxazole, and chromen-4-one analogues of the potent antitumor agent 2-(3,4-dimethoxyphenyl)-5-fluorobenzothiazole (PMX 610, NSC 721648). J Med Chem 2008; 51(16): 5135-9.
[http://dx.doi.org/10.1021/jm800418z] [PMID: 18666770]
[14]
Mir F, Shafi S, Zaman MS, et al. Sulfur rich 2-mercaptobenzothiazole and 1,2,3-triazole conjugates as novel antitubercular agents. Eur J Med Chem 2014; 76: 274-83.
[http://dx.doi.org/10.1016/j.ejmech.2014.02.017] [PMID: 24589483]
[15]
Paramashivappa R, Phani Kumar P, Subba Rao PV, Srinivasa Rao A. Design, synthesis and biological evaluation of benzimidazole/benzothiazole and benzoxazole derivatives as cyclooxygenase inhibitors. Bioorg Med Chem Lett 2003; 13(4): 657-60.
[http://dx.doi.org/10.1016/S0960-894X(02)01006-5] [PMID: 12639552]
[16]
Venkatesh P, Pandeya SN. Synthesis, characterization and anti-inflammatory activity of some 2-amino benzothiazole derivatives. J Chem Tech 2009; 1(4): 1354-8.Available From:. http://citeseerx.ist.psu.edu/viewdoc/summary?doi=10.1.1.608.7244
[17]
Hublikar MG, Dixit P, Kadu VD, et al. Synthesis of some novel (E)-methyl 2,4-dimethyl-5- (3-oxo-3- phenylprop-1-en-1-yl)-1H-pyrrole-3-carboxylate derivatives as antimicrobial agent. Asian J Pharm Clin Res 2019; 12(2): 4-9. Available From:
[http://dx.doi.org/10.22159/ajpcr.2019.v12i2.30275]
[18]
Kadu VD, Hublikar MG, Raut DG, Bhosale RB. Water-mediated ceric ammonium nitrate catalyzed C-C/C-N bond formation: Convenient access to polyfunctionalized pyrazoles via multicomponent reaction. Asian J Chem 2019; 31(5): 1189-94.
[http://dx.doi.org/10.14233/ajchem.2019.21947]
[19]
Lin L, Liu H, Wang D-J, Hu Y-J, Wei X-H. Synthesis and biological activities of 3,6-disubstituted-1,2,4- triazolo-1,3,4-thiadiazole. Bull Chem Soc Ethiop 2017; 31(3): 481-9.
[http://dx.doi.org/10.4314/bcse.v31i3.12]
[20]
Imran M, Bakht MA, Samad A. Abida. Synthesis of some quinoline-pyrazoline-based naphthalenyl thiazole derivatives and their evaluation as potential antimicrobial agents. Trop J Pharm Res 2017; 16(5): 1147-55.
[http://dx.doi.org/10.4314/tjpr.v16i5.24]
[21]
Gupta S, Ajmera N. Novel synthesis and biological activity study of pyrimido [2,1-b] benzothiazoles. Indian J Chem 2009; 48B: 853-8.
[22]
Zuo Y, Yang SG, Luo YP, et al. Design and synthesis of 1-(benzothiazol-5-yl)-1H-1,2,4-triazol-5-ones as protoporphyrinogen oxidase inhibitors. Bioorg Med Chem 2013; 21(11): 3245-55.
[http://dx.doi.org/10.1016/j.bmc.2013.03.056] [PMID: 23623257]
[23]
Vongtau HO, Abbah J, Mosugu O, et al. Antinociceptive profile of the methanolic extract of Neorautanenia mitis root in rats and mice. J Ethnopharmacol 2004; 92(2-3): 317-24.
[http://dx.doi.org/10.1016/j.jep.2004.03.014] [PMID: 15138018]
[24]
Cadenas E, Davies KJ. Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med 2000; 29(3-4): 222-30.
[http://dx.doi.org/10.1016/S0891-5849(00)00317-8] [PMID: 11035250]
[25]
Finkel T, Holbrook NJ. Oxidants, oxidative stress and the biology of ageing. Nature 2000; 408(6809): 239-47.
[http://dx.doi.org/10.1038/35041687] [PMID: 11089981]
[26]
Leelaprakash G. Mohan Dass. S. In vitro anti-inflammatory activity of methanol extract of Enicostemma axillare. Int J Drug Dev & Res 2010; 3: 189-96.
[27]
Sastre J, Pallardó FV, Viña J. The role of mitochondrial oxidative stress in aging. Free Radic Biol Med 2003; 35(1): 1-8.
[http://dx.doi.org/10.1016/S0891-5849(03)00184-9]
[28]
Ziakas GN, Rekka EA, Gavalas AM, Eleftheriou PT, Kourounakis PN. New analogues of butylated hydroxytoluene as anti-inflammatory and antioxidant agents. Bioorg Med Chem 2006; 14(16): 5616-24.
[http://dx.doi.org/10.1016/j.bmc.2006.04.030] [PMID: 16690318]
[29]
Lamson DW, Brignall MS. Antioxidants in cancer therapy; their actions and interactions with oncologic therapies. Altern Med Rev 1999; 4(5): 304-29.
[PMID: 10559547]
[30]
Gey KF. On the antioxidant hypothesis with regard to arteriosclerosis. Bibl Nutr Dieta 1986; 37(37): 53-91.
[PMID: 3510621]
[31]
Vivekananthan DP, Penn MS, Sapp SK, Hsu A, Topol EJ. Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet 2003; 361(9374): 2017-23.
[http://dx.doi.org/10.1016/S0140-6736(03)13637-9] [PMID: 12814711]
[32]
Raut DG, Lawand AS, Kadu VD, et al. Synthesis of asymmetric thiazolyl pyrazolines as a potential antioxidant and anti-inflammatory agents. Polycycl Aromat Compd 2020. (Article in press)
[http://dx.doi.org/10.1080/10406638.2020.1716028]
[33]
Jadhav SY, Bhosale RB, Shirame SP, Patil SB, Kulkarni SD. PEG mediated synthesis and biological evaluation of asymmetrical pyrazole curcumin analogues as potential analgesic, anti-inflammatory and antioxidant agents. Chem Biol Drug Des 2015; 85(3): 377-84.
[http://dx.doi.org/10.1111/cbdd.12416]
[34]
Bandgar BP, Adsul LK, Chavan HV, et al. Synthesis, biological evaluation, and docking studies of 3-(substituted)-aryl-5-(9-methyl-3-carbazole)-1H-2-pyrazolines as potent anti-inflammatory and antioxidant agents. Bioorg Med Chem Lett 2012; 22(18): 5839-44.
[http://dx.doi.org/10.1016/j.bmcl.2012.07.080] [PMID: 22901385]
[35]
Jadhav SY, Shirame SP, Kulkarni SD, Patil SB, Pasale SK, Bhosale RB. PEG mediated synthesis and pharmacological evaluation of some fluoro substituted pyrazoline derivatives as antiinflammatory and analgesic agents. Bioorg Med Chem Lett 2013; 23(9): 2575-8.
[http://dx.doi.org/10.1016/j.bmcl.2013.02.105] [PMID: 23541672]
[36]
El-Sayed MA-A, Abdel-Aziz NI, Abdel-Aziz AA, El-Azab AS, ElTahir KE. Synthesis, biological evaluation and molecular modeling study of pyrazole and pyrazoline derivatives as selective COX-2 inhibitors and anti-inflammatory agents. Part 2. Bioorg Med Chem 2012; 20(10): 3306-16.
[http://dx.doi.org/10.1016/j.bmc.2012.03.044] [PMID: 22516672]
[37]
Bandgar BP, Gawande SS, Bodade RG, Gawande NM, Khobragade CN. Synthesis and biological evaluation of a novel series of pyrazole chalcones as anti-inflammatory, antioxidant and antimicrobial agents. Bioorg Med Chem 2009; 17(24): 8168-73.
[http://dx.doi.org/10.1016/j.bmc.2009.10.035] [PMID: 19896853]
[38]
Bhatia MS, Pakhare KB. 2D QSAR and docking of novel N-substituted aryl amine derivatives as potential inhibitors of Lumazine synthase. Lat Am J Pharm 2010; 29(3): 362-8.
[39]
Choudhari PB, Bhatia MS. Pharmacophore modeling and 3D QSAR studies of aryl amine derivatives as potential Lumazine synthase inhibitors. Arabian J Chem 2017; 10(1): S100-4.
[http://dx.doi.org/10.1016/j.arabjc.2012.05.008]
[40]
Choudhari PB, Bhatia MS. 3D QSAR, docking studies and pharmacophore modeling of selected factor Xa inhibitors. Med Chem Res 2012; 21: 1427-32.
[http://dx.doi.org/10.1007/s00044-011-9663-8]
[41]
Molinspiration cheminformatics software Available from: http://www.molinspiration.com/services/properties.html (accessed 17.01.17).
[42]
Zhao YH, Abraham MH, Le J, et al. Rate-limited steps of human oral absorption and QSAR studies. Pharm Res 2002; 19(10): 1446-57.
[http://dx.doi.org/10.1023/A:1020444330011] [PMID: 12425461]

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