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Recent Advances in Inflammation & Allergy Drug Discovery

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ISSN (Print): 2772-2708
ISSN (Online): 2772-2716

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Research Article

A Novel Method for the Syntheses of Imidazo-Thiadiazoles as Potential Antioxidants and Anti-Inflammatory Agents

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

Volume 16, Issue 1, 2022

Published on: 15 July, 2022

Page: [19 - 25] Pages: 7

DOI: 10.2174/2772270816666220410130059

Price: $65

Abstract

Background: A literature survey revealed that many imidazo-thiadiazole molecules were used as key intermediates for the development of novel drugs. The synthesized imidazo-thiadiazole derivatives were tested for their in vitro antioxidant and anti-inflammatory properties. The purpose of this research paper is to provide readers with information regarding diseases caused by free radicals.

Objective: The objective of this study is to develop novel antioxidant and anti-inflammatory drugs.

Methods: Imidazo-thiadiazole derivatives 5a-f were synthesized through cyclo-condensation reactions in two steps. First, the synthesis of 2-amino-thiadiazole derivatives from substituted aromatic carboxylic acids and thiosemicarbazide by using POCl3 as a solvent as well as a catalyst was performed. In the next step, imidazo-thiadiazoles were prepared from 2-amino-thiadiazole derivatives with appropriate α-haloketones in the presence of polyethylene glycol-300 (PEG-300) as a green solvent. These imidazo- thiadiazole derivatives were prepared by using a novel method. The synthesized compounds were in vitro tested for their antioxidant and anti-inflammatory activities.

Results: In vitro evaluation report showed that nearly all molecules possess potential antioxidant activity against 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO), superoxide radical (SOR), and hydrogen peroxide (H2O2) radical scavenging activity. Most of the imidazo-thiadiazole derivatives have shown significant anti-inflammatory activity as compared to diclofenac sodium as a reference standard.

Conclusion: In the search for novel therapies to treat inflammation and oxidation, we have made efforts to develop anti-inflammatory and antioxidant agents with a preeminent activity. Imidazo-thiadiazoles 5a, 5e as well as 5f showed potential anti-inflammatory activity. All tested imidazo-thiadiazole derivatives (5a-f) showed potential antioxidant activity against one more radical scavenging species as compared to ascorbic acid as the reference standard. Thus, imidazo-thiadiazole derivatives constitute an interesting template for the design and development of new antioxidant as well as anti-inflammatory agents.

Keywords: Biological evaluations, antioxidant activity, anti-inflammatory activity, imidazo thiadiazoles derivatives, bis-imidazo thiadiazoles derivatives, polycyclic aromatic compounds.

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[1]
Schmid-Schönbein GW. Analysis of inflammation. Annu Rev Biomed Eng 2006; 8(1): 93-131.
[http://dx.doi.org/10.1146/annurev.bioeng.8.061505.095708] [PMID: 16834553]
[2]
Ingle PV, Patel DM. C-reactive protein in various disease condition – An overview. Asian J Pharm Clin Res 2011; 4: 9-13.
[3]
Bergink V, Gibney SM, Drexhage HA. Autoimmunity, inflammation, and psychosis: a search for peripheral markers. Biol Psychiatry 2014; 75(4): 324-31.
[http://dx.doi.org/10.1016/j.biopsych.2013.09.037] [PMID: 24286760]
[4]
Böhm R, Proksch E, Schwarz T, Cascorbi I. Arzneimittelüberempfindlichkeit: Diagnostik, genetik und vermeidung. Dtsch Arztebl Int 2018; 115(29–30): 501-12.
[http://dx.doi.org/10.3238/arztebl.2018.0501]
[5]
Mizushima Y. Simple screening test for antirheumatic drugs. Lancet 1965; 285(7377): 169-70.
[http://dx.doi.org/10.1016/S0140-6736(65)91134-7]
[6]
Fascio ML, Sepúlveda CS, Damonte EB, D’Accorso NB. Synthesis and antiviral activity of some imidazo[1,2-b][1,3,4]thiadiazole carbohydrate derivatives. Carbohydr Res 2019; 480(480): 61-6.
[http://dx.doi.org/10.1016/j.carres.2019.05.003]
[7]
Sanfilippo PJ, Urbanski M, Press JB, Dubinsky B, Moore JB. Synthesis of (Aryloxy)alkylamines. 2. Novel imidazo-fused heterocycles with calcium channel blocking and local anesthetic activity. J Med Chem 1988; 31(11): 2221-7.
[http://dx.doi.org/10.1021/jm00119a026]
[8]
Tahghighi A, Babalouei F. Thiadiazoles: The appropriate pharmacological scaffolds with leishmanicidal and antimalarial activities: A review. Iran J Basic Med Sci 2017; 20(6): 613-22.
[http://dx.doi.org/10.22038/IJBMS.2017.8828]
[9]
Barnish IT, Cross PE, Dickinson RP, Gadsby B, Parry MJ, Randall MJ. Cerebrovasodilatation through selective inhibition of the enzyme carbonic anhydrase. 2. Imidazo[2, 1-b]thiadiazole and imidazo[2, 1-b]thiazolesulfonamides. J Med Chem 1980; 23(2): 117-21.
[http://dx.doi.org/10.1021/jm00176a003]
[10]
Patel HM, Noolvi MN, Goyal A, Thippeswamy BS. 2,5,6-trisubstituted imidazo[2,1-b][1,3,4]thiadiazoles: Search for antihyperlipidemic agents. Eur J Med Chem 2013; 65: 119-33.
[http://dx.doi.org/10.1016/j.ejmech.2013.04.020] [PMID: 23707917]
[11]
Kumar S, Gopalakrishnan V, Hegde M, Rana V, Dhepe SS, Ramareddy SA. Synthesis and antiproliferative activity of imidazo[2,1-b][1,3,4]thiadiazole derivatives. Bioorg Med Chem Lett 2014; 24(19): 4682-8.
[http://dx.doi.org/10.1016/j.bmcl.2014.08.032]
[12]
Romagnoli R, Baraldi PG, Prencipe F, Balzarini J, Liekens S, Estévez F. Design, synthesis and antiproliferative activity of novel heterobivalent hybrids based on imidazo[2,1-b][1,3,4]thiadiazole and imidazo[2,1-b][1,3]thiazole scaffolds. Eur J Med Chem 2015; 101: 205-17.
[http://dx.doi.org/10.1016/j.ejmech.2015.06.042] [PMID: 26141911]
[13]
Noolvi MN, Patel HM, Kamboj S, Kaur A, Mann V. 2,6-Disubstituted imidazo[2,1-b][1,3,4]thiadiazoles: Search for anticancer agents. Eur J Med Chem 2012; 56: 56-69.
[http://dx.doi.org/10.1016/j.ejmech.2012.08.012] [PMID: 22960694]
[14]
Gadad A, Karki S, Rajurkar V, Bhongade B. Synthesis and biological evaluation of 5-formyl-6-arylimidazo(2,1-b)-1,3,4-thiadiazole-2-N(dimethylaminomethino)sulfonamides as antitumor agents. Arzneimittelforschung 2011; 49(10): 858-63.
[http://dx.doi.org/10.1055/s-0031-1300515]
[15]
Terzioglu N, Gürsoy A. Synthesis and anticancer evaluation of some new hydrazone derivatives of 2,6-dimethylimidazo[2,1-b][1,3,4]thiadiazole-5-carbohydrazide. Eur J Med Chem 2003; 38(7–8): 781-6.
[http://dx.doi.org/10.1016/S0223-5234(03)00138-7]
[16]
Raut DG, Patil SB, Kadu VD, Hublikar MG, 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]
[17]
Karki SS, Panjamurthy K, Kumar S, et al. Synthesis and biological evaluation of novel 2-aralkyl-5-substituted-6-(4′-fluorophenyl)-imidazo[2,1-b][1,3,4]thiadiazole derivatives as potent anticancer agents. Eur J Med Chem 2011; 46(6): 2109-16.
[http://dx.doi.org/10.1016/j.ejmech.2011.02.064] [PMID: 21439690]
[18]
Taher AT, Georgey HH, El-Subbagh HI. Novel 1,3,4-heterodiazole analogues: Synthesis and in-vitro antitumor activity. Eur J Med Chem 2012; 47(1): 445-51.
[http://dx.doi.org/10.1016/j.ejmech.2011.11.013] [PMID: 22119151]
[19]
Khazi IAM, Mahajanshetti CS, Gadad AK, Tarnalli AD, Sultanpur CM. Synthesis, anticonvulsant and analgesic activities of some 6-substituted imidazo(2,1-b)-1,3,4-thiadiazole-2-sulfonamides and their 5-bromo derivatives. Arzneimittelforschung 1996; 46(10): 949-52.
[http://dx.doi.org/10.1002/chin.199711111] [PMID: 8931885]
[20]
Alegaon SG, Alagawadi KR, Sonkusare PV, Chaudhary SM, Dadwe DH, Shah AS. Novel imidazo[2,1-b][1,3,4]thiadiazole carrying rhodanine-3-acetic acid as potential antitubercular agents. Bioorg Med Chem Lett 2012; 22(5): 1917-21.
[http://dx.doi.org/10.1016/j.bmcl.2012.01.052] [PMID: 22325950]
[21]
Kolavi G, Hegde V, Khazi Ia, Gadad P. Synthesis and evaluation of antitubercular activity of imidazo[2,1-b][1,3,4]thiadiazole derivatives. Bioorg Med Chem 2006; 14(9): 3069-80.
[http://dx.doi.org/10.1016/j.bmc.2005.12.020] [PMID: 16406644]
[22]
Gadad AK, Noolvi MN, Karpoormath RV. Synthesis and anti-tubercular activity of a series of 2-sulfonamido/trifluoromethyl-6-substituted imidazo[2,1-b]-1,3,4-thiadiazole derivatives. Bioorg Med Chem 2004; 12(21): 5651-9.
[http://dx.doi.org/10.1016/j.bmc.2004.07.060] [PMID: 15465343]
[23]
Alwan WS, Karpoormath R, Palkar MB, et al. Novel imidazo[2,1-b]-1,3,4-thiadiazoles as promising antifungal agents against clinical isolate of Cryptococcus neoformans. Eur J Med Chem 2015; 95: 514-25.
[http://dx.doi.org/10.1016/j.ejmech.2015.03.021] [PMID: 25847769]
[24]
Jadhav VB, Kulkarni MV, Rasal VP, Biradar SS, Vinay MD. Synthesis and anti-inflammatory evaluation of methylene bridged benzofuranyl imidazo[2,1-b][1,3,4]thiadiazoles. Eur J Med Chem 2008; 43(8): 1721-9.
[http://dx.doi.org/10.1016/j.ejmech.2007.06.023] [PMID: 17845827]
[25]
Gadad AK, Palkar MB, Anand K, Noolvi MN, Boreddy TS, Wagwade J. Synthesis and biological evaluation of 2-trifluoromethyl/sulfonamido-5,6-diaryl substituted imidazo[2,1-b]-1,3,4-thiadiazoles: A novel class of cyclooxygenase-2 inhibitors. Bioorg Med Chem 2008; 16(1): 276-83.
[http://dx.doi.org/10.1016/j.bmc.2007.09.038] [PMID: 17937989]
[26]
Abignente E, Arena F, Luraschi E, et al. Research on heterocyclic compounds. XVIII. Imidazo[2,1-b]-1,3,4-thiadiazole derivatives. Farmaco, Sci 1985; 40(3): 190-9.
[PMID: 3874092]
[27]
Marin A, Valls N, Berenguer FJ, et al. Synthesis and anthelmintic activity of carbamates derived from imidazo[2,1-b][1,3,4]thiadiazole and imidazo[2,1-b]thiazole. Farmaco 1992; 47(1): 63-75.
[PMID: 1616578]
[28]
Raut DG, Kadu VD, Sonawane VD, Bhosale RB. Synthesis of thiazole scaffolds by novel method and their in vitro anthelmentic activity against Indian adult earthworm. Eur J Biomed Pharm Sci 2015; 2(4): 922-31.
[29]
Bhongade BA, Talath S, Gadad RA, Gadad AK. Biological activities of imidazo[2,1-b][1,3,4]thiadiazole derivatives: A review. J Saudi Chem Soc 2016; 20: S463-75.
[http://dx.doi.org/10.1016/j.jscs.2013.01.010]
[30]
Andreani A, Rambaldi M, Locatelli A, Bossa R, Salvatore G, Galatulas I. Synthesis and cardiotonic activity of aryl- or pyridyl-substituted fused imidazoles. Eur J Med Chem 1994; 29(5): 339-42.
[http://dx.doi.org/10.1016/0223-5234(94)90057-4]
[31]
Alexandria FA. -. Synthesis of some phenoxymethylbenzimidazole derivatives as potential antibacterial and antifungal agents. J Pharm Sci 1991; 5(1): 16-20.
[32]
Khazi IAM, Gadad AK, Lamani RS, Bhongade BA. Chemistry of imidazo[2,1-b][1,3,4]thiadiazoles. Tetrahedron 2011; 67(19): 3289-316.
[http://dx.doi.org/10.1016/j.tet.2011.03.027]
[33]
Kadu VD, Chandrudu SN, Hublikar MG, Raut DG, Bhosale RB. Metal-free oxidative coupling of arylmethylamines with indoles: A simple, environmentally benign approach for the synthesis of 3,3′-bis(indolyl)methanes. RSC Advances 2020; 10(39): 23254-62.
[http://dx.doi.org/10.1039/D0RA03221B]
[34]
Hublikar M, Dixit P, Kadu V, 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.
[http://dx.doi.org/10.22159/ajpcr.2019.v12i2.30275]
[35]
Kadu VD, Nadimetla DN, Hublikar MG, Raut DG, Bhosale RB. Water-mediated green and efficient synthesis of bis(indolyl)methanes using ammonium iron(ii) sulfate. Lett Org Chem 2020; 17(1): 61-7.
[http://dx.doi.org/10.2174/1570178616666190522121135]
[36]
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]
[37]
Farrokhnia M. Density functional theory studies on the antioxidant mechanism and electronic properties of some bioactive marine meroterpenoids: Sargahydroquionic acid and sargachromanol. ACS Omega 2020; 5(32): 20382-90.
[http://dx.doi.org/10.1021/acsomega.0c02354] [PMID: 32832791]
[38]
Pari S, Wang IA, Liu H, Wong BM. Sulfate radical oxidation of aromatic contaminants: A detailed assessment of density functional theory and high-level quantum chemical methods. Environ Sci Process Impacts 2017; 19(3): 395-404.
[http://dx.doi.org/10.1039/C7EM00009J] [PMID: 28229155]
[39]
Kumar RS, Sivakumar T, Sundaram RS, Sivakumar P, Nethaji R, Gupta M, et al. Antimicrobial and antioxidant activities of Careya arborea Roxb. stem bark. Iran J Pharmacol Ther 2006; 5(1): 35-41.
[40]
Raut DG, Patil SB, Choudhari PB, et al. POCl 3 mediated syntheses, pharmacological evaluation and molecular docking studies of some novel benzofused thiazole derivatives as a potential antioxidant and anti-inflammatory agents. Curr Chem Biol 2020; 14(1): 58-68.
[http://dx.doi.org/10.2174/2212796813666191118100520]
[41]
Gülçin I, Alici HA, Cesur M. Determination of in vitro antioxidant and radical scavenging activities of propofol. Chem Pharm Bull (Tokyo) 2005; 53(3): 281-5.
[http://dx.doi.org/10.1248/cpb.53.281] [PMID: 15744098]
[42]
Hublikar M, Kadu V, Dublad JK, et al. (E)-2-(2-Allylidenehydrazinyl)thiazole derivatives: Design, green synthesis, in silico and in vitro antimycobacterial and radical scavenging studies. Arch Pharm (Weinheim) 2020; 353(7): e2000003.
[http://dx.doi.org/10.1002/ardp.202000003] [PMID: 32372473]
[43]
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]
[44]
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; 42(1): 1-10.
[http://dx.doi.org/10.1080/10406638.2020.1716028]
[45]
El-Sayed MAA, Abdel-Aziz NI, Abdel-Aziz AAM, El-Azab AS, ElTahir KEH. 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]

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