Synthesis Under Microwave Irradiation and Molecular Docking of Some Novel Bioactive Thiadiazoles

Author(s): Sobhi M. Gomha*, Mastora M. Edress, Zeinab A. Muhammad*, Hatem M. Gaber, Mohamed M. Amin, Islam K. Matar

Journal Name: Mini-Reviews in Medicinal Chemistry

Volume 19 , Issue 5 , 2019

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Graphical Abstract:


Background: A novel series of fused imidazole was prepared from the reaction of 2- bromoacetyl-3-phenyl-1,3,4-thiadiazole with various heterocyclic amines under microwave irradiation. The structures of all the novel products were elucidated based on the elemental analysis and spectral data.

Results: In addition, the biological activity of the newly synthesized compounds was evaluated and the results obtained indicate their potency as anti-inflammatory, analgesic and anti- ulcer agents.

Conclusion: The binding mechanism of the most active compounds was studied using MOE to analyze the molecular interactions.

Keywords: 1, 3, 4-thiadiazoles, fused imidazoles, heterocyclic amines, microwave irradiation, anti-inflammatory, analgesic and anti-ulcer agents.

Supuran, C.T.; Briganti, F.; Tilli, S.; Chegwidden, W.R.; Scozzafava, A. A Carbonic anhydrase inhibitors: Sulfonamides as antitumor agents. Bioorg. Med. Chem., 2001, 9, 703-714.
Liu, X.; Shi, Y.; Ma, Y.; Zhang, C.; Dong, W.; Pan, L.; Wang, B.; Li, Z. Synthesis, antifungal activities and 3D-QSAR study of N-(5-substituted-1, 3, 4-thiadiazol-2-yl) cyclopropane-carboxamides. Eur. J. Med. Chem., 2009, 44, 2782-2789.
Holla, B.S.; Poorjary, K.N.; Rao, B.S.; Shivananda, M.K. New bis-aminomercaptotriazoles and bis-triazolothiadiazoles as possible anticancer agents. Eur. J. Med. Chem., 2002, 37, 511-520.
Siddiqui, N.; Ahuja, P.; Ahsan, W.; Pandeya, S.N.; Alam, M.S. Thiadiazoles: Progress report on biological activities. J. Chem. Pharm. Res., 2009, 1, 19-29.
Barbuceanu, S.F.; Almajan, G.L. New heterocyclic compounds from 1,2 4-triazole and 1,3,4-thiadiazole class having diphenylsulphone and 2-fluorophenyl fragments. Rev. Chim, 2011, 62, 308-312.
Burbuliene, M.M.; Sakociute, V.; Vainilavicius, P. Synthesis and characterization of new pyrimidine-based 1, 3, 4-oxa (thia) diazoles, 1, 2, 4-triazoles and 4-thiazolidinones. Arkivoc, 2009, 12, 281-289.
Kadi, A.; El-Brollosy, N.R.; Al-Deeb, O.A.; Habib, E.E.; Ibrahim, T.M.; El-Emam, A.A. Synthesis, antimicrobial, and anti-inflammatory activities of novel 2-(1-adamantyl)-5-substituted-1,3,4-oxadiazoles and 2-(1-adamantylamino)-5-substituted-1,3,4-thiadiazoles. Eur. J. Med. Chem., 2007, 42, 235-242.
Amir, M.; Kumar, S. Synthesis and evaluation of anti-inflammatory, analgesic, ulcerogenic and lipid peroxidation properties of ibuprofen derivatives. Acta Pharm., 2007, 57, 31-45.
Meena, D.R.; Maiti, B.; Chanda, K. Cu(I) catalyzed microwave assisted telescopic synthesis of 3,5-disubstituted isoxazoles in green media. Tetrahedron Lett., 2016, 57, 5514-5517.
Balwe, S.G.; Shinde, V.V.; Jeong, Y.T. Iron-catalyzed microwave-promoted expeditiousone-pot synthesis of benzo[b][1,4]thiazine-4-carbonitrile under solvent-free condition. Tetrahedron Lett., 2016, 57, 5074-5078.
Abbas, E.M.H.; Gomha, S.M.; Farghaly, T.A. Multicomponent reactions for synthesis of bioactive polyheterocyclic ring systems under controlled microwave irradiation. Arab. J. Chem., 2014, 7, 623-629.
Gomha, S.M.; Riyadh, S.M. Synthesis of triazolo[4,3-b][1,2,4,5]tetrazines and triazolo[3,4-b][1,3,4]thiadiazines using chitosan as ecofriendly catalyst under microwave irradiation. Arkivoc, 2009, xi, 58-68.
Gomha, S.M.; Eldebss, T.M.A.; Badrey, M.G.; Abdulla, M.M.; Mayhoub, A.S. Novel 4-Heteroaryl-Antipyrines as DPP-IV Inhibitors. Chem. Biol. Drug Des., 2015, 86, 1292-1303.
Gomha, S.M.; Riyadh, S.M. Synthesis under microwave irradiation of [1,2,4]triazolo-[3,4-b][1,3,4]thiadiazoles and other diazoles bearing indole moieties and their antimicrobial evaluation. Molecules, 2011, 16, 8244-8256.
Gomha, S.M.; Edrees, M.M.; Faty, R.A.M.; Muhammad, Z.A.; Mabkhot, Y.N. Microwave-assisted one pot three-component synthesis of some novel pyrazole scaffolds as potent anticancer agents. Chem. Cent. J., 2017, 11,37(1-12)
Abdel-Aziz, H.A.; Gomha, S.M. A new aspect of the Pfitzinger reaction: Microwave-assisted synthesis of the new heterocyclic ring system 6-arylbenzo[4,5]imidazolo[2,1-b]quino[4,3-e]-1,3-thiazin-14-one. Z. Naturforsch., 2009, 64b, 826-830.
Gomha, S.M.; Riyadh, S.M.; Abdalla, M.M. Solvent-drop grinding method: Efficient synthesis, DPPH radical scavenging and anti-diabetic activities of chalcones, bis-chalcones, azolines, and bis-azolines. Curr. Org. Synth., 2015, 12, 220-228.
Gomha, S.M.; Badrey, M.G. Edrees, M.M. Heterocyclization of a bis-thiosemicarbazone of 2,5-diacetyl-3,4-disubstituted-thieno[2,3-b]thiophene bis-thiosemicarbazones leading to bis-thiazoles and bis-1,3,4-thiadiazoles as anti-breast cancer agents. J. Chem. Res., 2016, 40, 120-125.
Gomha, S.M.; Khalil, K.D.; El-Zanate, A.M.; Riyadh, S.M. A Facile Green Synthesis and anti-cancer activity of bisarylhydrazononitriles, triazolo[5,1-c][1,2,4]triazine, and 1,3,4- thiadiazoline. Heterocycles, 2013, 87, 1109-1120.
Gomha, S.M.; Abdelrazek, F.M.; Abdelrahman, A.H.; Metz, P. Synthesis of some novel thiazole, thiadiazole and 1,4-phenylene-bis-thiazole derivatives. Heterocycles, 2016, 92, 954-967.
Gomha, S.M. A facile one-pot synthesis of 6,7,8,9-tetrahydrobenzo[4,5]thieno[2,3-d]-1,2,4-triazolo[4,5-a]pyrimidin-5-ones. Monatsh. Chem., 2009, 140, 213-220.
Gomha, S.M.; Riyadh, S.M.; Abbas, I.M.; Bauomi, M.A. Synthetic utility of ethylidenethiosemicarbazide: Synthesis and anticancer activity of 1,3-thiazines and thiazoles with imidazole moiety. Heterocycles, 2013, 87, 341-356.
Gomha, S.M.; Abdel-aziz, H.M.; Khalil, K.D. Synthesis and SAR study of the novel thiadiazole-imidazole derivatives as new anti-cancer agents. Chem. Pharm. Bull., 2016, 64, 1356-1363.
Gomha, S.M.; Eldebss, T.M.A.; Abdulla, M.M.; Mayhoub, A.S. Diphenylpyrroles: Novel p53 activators. Eur. J. Med. Chem., 2014, 82, 472-479.
Gomha, S.M.; Edrees, M.M.; Altalbawy, F.M.A. Synthesis and characterization of some new bis-pyrazolyl-thiazoles incorporating the thiophene moiety as potent anti-tumor agents. Int. J. Mol. Sci., 2016, 17(1499), 1-12.
Gomha, S.M.; Salah, T.A.; Abdelhamid, A.O. Synthesis, characterization and pharmacological evaluation of some novel thiadiazoles and thiazoles incorporating pyrazole moiety as potent anticancer agents. Monatsh. Chem., 2015, 146, 149-158.
Abdalla, M.A.; Gomha, S.M.; Abdelaziz, M.; Serag, N. Synthesis and antiviral evaluation of some novel thiazoles and 1,3-thiazines substituted with pyrazole moiety against rabies virus. Turk. J. Chem., 2016, 40, 441-453.
Farghaly, T.A.; Abdallah, M.A.; Muhammad, Z.A. Synthesis and evaluation of the anti-microbial activity of new heterocycles containing the 1,3,4-Thiadiazole moiety. Molecules, 2011, 16, 10420-10432.
Gomha, S.M.; Shawali, A.S.; Abdelhamid, A.O. Convenient method for synthesis of various fused heterocycles via utility of 4-acetyl-5-methyl-1-phenyl-pyrazole as precursor. Turk. J. Chem., 2014, 38, 865-879.
Abdallah, M.A.; Riyadh, S.M.; Abbas, I.M.; Gomha, S.M. Synthesis and biological activities of 7-arylazo-7H-pyrazolo[5,1-c][1,2,4]triazolo-6(5H)-ones and 7-arylhydrazono-7H-[1,2,4]triazolo [3,4-b][1,3,4] thiadiazines. J. Chin. Chem. Soc., 2005, 52, 987-994.
Dawood, K.M.; Gomha, S.M. Synthesis and anti-cancer activity of 1,3,4-thiadiazole and 1,3-thiazole derivatives having 1,3,4-oxadiazole moiety. J. Heterocycl. Chem., 2015, 52, 1400-1405.
Woolfe, C.; Macdonald, A.D. The evaluation of the analgesic action of pethidine hydrochloride (demerol). J. Pharmacol. Exp. Ther., 1944, 80, 300-307.
Koriem, K.M.; Asaad, G.F.; Megahed, H.A.; Zahran, H.; Arbid, M.S. Evaluationof the antihyperlipidemic, anti-inflammatory, analgesic, and antipyreticactivities of ethanolic extract of Ammi majus seeds in Albino rats and mice. Intl. J. Toxicol., 2012, 31, 294-300.
Amin, M.M.; Arbid, M.S. Estimation of the novel antipyretic, anti-inflammatory, antinociceptive and antihyperlipidemic effects of silymarin in Albino rats and mice. Asian Pacific . J. Trop. Biomed., 2015, 5, 619-623.
Eddy, N.B.; Touchberry, C.F.; Lieberman, J.E. Synthetic analgesics methadone isomers and derivatives. J. Pharmacol. Exp. Ther., 1950, 98, 121-137.
Winter, C.A.; Risley, E.A.; Nuss, G.W. Carrageenin-induced edema in hindpaws of the rat as an assay for anti-inflammatory drugs. Proc. Soc. Exp. Biol. Med., 1962, 111, 544-547.
Prempeh, A.B.A.; Mensah-Attipoe, J. Inhibition of vascular response ininflammation by crude aqueous extract of the root bark of Zanthoxylumxanthoxyloides. Ghana Med. J., 2009, 43, 77-81.
Sudjarwo, S.A. The potency of piperine as antiinflammatory andanalgesic in rats and mice. Folia Med. Indones, 2005, 41, 190-194.
Sayanti, B.; Susri, R.C.; Subrata, C.; Sandip, K.B. Healing properties of some Indian medicinal plants against indomethacin-induced gastriculceration of rats. J. Clin. Biochem. Nutr., 2007, 41, 106-114.
Szabo, S.; Hollander, D. Pathways of gastrointestinal protection andrepair: Mechanisms of action of sucralfate. Am. J. Med., 1985, 86, 23-31.
Wang, J.L.; Limburg, D.; Graneto, M.J.; Springer, J.; Hamper, J.R.B.; Liao, S.; Pawlitz, J.L.; Kurumbail, R.G.; Maziasz, T.; Talley, J.J.; Kiefer, J.R. The novel benzopyran class of selective cyclooxygenase-2 inhibitors. Part 2: The second clinical candidate having a shorter and favorable human half-life. Bioorg. Med. Chem. Lett., 2010, 20, 7159-7163.
Wallace, J.L.; Devchand, P.R. Emerging roles for cyclooxygenase‐2 in gastrointestinal mucosal defense. Brit. J. Pharmacol., 2005, 145, 275-282.
Ryn, J.V.; Trummlitz, G.; Pairet, M. COX-2 selectivity and inflammatory processes. Curr. Med. Chem., 2000, 7, 1145-1161.
Dhanjal, J.K.; Sreenidhi, A.K.; Bafna, K.; Katiyar, S.P.; Goyal, S.; Grover, A.; Sundar, D. Computational structure-based de novo design of hypothetical inhibitors against the anti-inflammatory target COX-2. PloS one, 2015, 10, e0134691.
Eweiss, N.F.; Osman, A.O. Synthesis of heterocycles. Part II. New routes to acetylthiadiazolines and alkylazothiazoles. J. Heterocycl. Chem., 1980, 17, 1713-1717.

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Article Details

Year: 2019
Published on: 21 February, 2019
Page: [437 - 447]
Pages: 11
DOI: 10.2174/1389557518666180329122317
Price: $65

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