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Letters in Drug Design & Discovery


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

Research Article

Novel 1,3,4-Oxadiazole Fused Thiadiazole Derivatives: Synthesis and study of Anticancer Activities

Author(s): Zanjam Spandana, Reddymasu Sreenivasulu, Tadigiri MalathiRekha and Mandava Venkata Basaveswara Rao*

Volume 16, Issue 6, 2019

Page: [656 - 662] Pages: 7

DOI: 10.2174/1570180816666181031125946

Price: $65


Background: In search of novel anticancer agents, a series of 1,3,4-oxadiazole derivatives (12a-j) containing 1,3,4-thiadiazole moieties were synthesized, and their structures were confirmed by 1HNMR, 13CNMR and ESI-MS spectral analysis.

Methods: Cytotoxicity of these compounds was evaluated by MTT assay in vitro against four human tumor cell lines, i.e. A549 (lung), MCF-7 (breast), A375 (melanoma) and HT-29 (colon).

Results: Here, CA4 used as positive control. Among them, compounds 12b, 12c, 12f, 12g, 12h and 12j were exhibited promising activity than control drug.

Conclusion: In conclusion, we have synthesized a novel series of 1,3,4-oxadiazole fused 1,3,4- thiazdiazole derivatives and their structures were confirmed by spectral analysis.

Keywords: Methazolamide, megazol, zibotentan, MTT assay, anticancer activity, melanoma.

Graphical Abstract
“Cancer Fact sheet No297”. World Health Organization. February 2014. 10 June 2014.
“Defining Cancer”. National Cancer Institute. 10 June 2014.
World Cancer Report 2014. World Health Organization. 2014. Pp. Chapter 1.1. ISBN 9283204298.
"The top 10 causes of death Fact sheet N°310". WHO. May 2014. 10 June2014.
Ali, R.; Mirza, Z.; Ashraf, G.M.; Kamal, M.A.; Ansari, S.A.; Damanhouri, G.A.; Abuzenadah, A.M.; Chaudhary, A.G.; Sheika, I.A. New anticancer agents: Recent developments in tumor therapy. Anticancer Res., 2012, 32(7), 2999-3005.
McCubrey, J.A.; Steelman, L.S.; Abrams, S.L.; Lee, J.T.; Chang, F.; Bertrand, F.E.; Navolanic, P.M.; Terrian, D.M.; Franklin, R.A.; D’Assoro, A.B.; Salishbury, J.L.; Mazzarino, M.C.; Stivala, F.; Libra, M. Roles of the RAF/MEK/ERK and P13K/PTEN /AKT pathways in malignant transformation and drug resistance. Adv. Enzyme Regul., 2006, 46, 249-279.
Sreedhar, A.S.; Csermely, P. Heat shock proteins in the regulation of apoptosis: New strategies in tumor therapy: A comprehensive review. Pharmacol. Ther., 2004, 101, 227-257.
Hatti, I.; Sreenivasulu, R.; Jadav, S.S.; Ahsan, M.J.; Raju, R.R. Synthesis and biological evaluation of 1,3,4-oxadiazole linked bis indole derivatives as anticancer agents. Monatsh. Chem., 2015, 146, 1699-1705.
Hatti, I.; Sreenivasulu, R.; Jadav, S.S.; Jayaprakash, V.; Kumar, C.G.; Raju, R.R. Synthesis, cytotoxic activity and docking studies of new 4 - aza podophyllotoxin derivatives. Med. Chem. Res., 2015, 24, 3305-3313.
Ahsan, M.J.; Choudhary, K.; Jadav, S.S.; Yasmin, S.; Ansari, M.Y.; Sreenivasulu, R. Synthesis, antiproliferative activity and molecular docking studies of curcumin analogues bearing pyrazole ring. Med. Chem. Res., 2015, 24, 4166-4180.
Reddy, N.B.; Burra, V.R.; Ravindranath, L.K.; Sreenivasulu, R.; Kumar, V.N. Synthesis and biological evaluation of benzoxazole fused combretastatin derivatives as anticancer agents. Monatsh. Chem., 2016, 147, 593-598.
Reddy, N.B.; Burra, V.R.; Ravindranath, L.K.; Kumar, V.N.; Sreenivasulu, R.; Sadanandam, P. Synthesis and biological evaluation of benzimidazole fused ellipticine derivatives as anticancer agents. Monatsh. Chem., 2016, 147, 599-604.
Sreenivasulu, R.; Sujitha, P.; Jadav, S.S.; Ahsan, M.J.; Kumar, C.G.; Raju, R.R. Synthesis, antitumor evaluation and molecular docking studies of Indole - Indazolyl hydrazide - hydrazone derivatives. Monatsh. Chem., 2017, 148, 305-314.
Madhavi, S.; Sreenivasulu, R.; Raju, R.R. Synthesis and biological evaluation of oxadiazole incorporated ellipticine derivatives as anticancer agents. Monatsh. Chem., 2017, 148, 933-938.
Agarwal, M.; Singh, V.; Sharma, S.C.; Sharma, P.; Ansari, Md. Y.; Jadav, S.S.; Yasmin, S.; Sreenivasulu, R.; Hassan, Md.H. Design and synthesis of new 2,5-disubstituted 1,3,4- oxadiazole analogues as anticancer agents. Med. Chem. Res., 2016, 25, 2289-2303.
Madhavi, S.; Sreenivasulu, R.; Jyotsna, Y.; Raju, R.R. Synthesis of Chalcone incorporated Quinazoline derivatives as Anticancer Agents. Saudi Pharm. J., 2017, 25, 275-279.
Madhavi, S.; Sreenivasulu, R.; Ansari, Md. Y.; Ahsan, M.J.; Raju, R.R. Synthesis, biological evaluation and molecular docking studies of pyridine incorporated chalcone derivatives as anticancer agents. Lett. Org. Chem., 2016, 13, 682-692.
Sreenivasulu, R.; Durgesh, R.; Jadav, S.S.; Sujitha, P.; Kumar, C.G.; Raju, R.R. Synthesis, anticancer evaluation and molecular docking studies of Bis(indolyl) triazinones, Nortopsentin analogues. Chem. Pap., 2018, 72, 1369-1378.
Subramanyam, M.; Sreenivasulu, R.; Rambabu, G.; Rao, M.V.B.; Rao, K.P. Synthesis, biological evaluation and docking studies of 1,3,4-Oxadiazole fused benzothiazole derivatives for anticancer drugs. Lett. Drug Des. Discov., 2018, 15(12), 1299-1307.
Durgesh, R.; Sreenivasulu, R.; Srinivasarao, P.; Raju, R.R. Synthesis and anticancer evaluation of indazole-aryl hydrazide-hydrazone derivatives. J. Indian Chem. Soc., 2018, 95, 1-6.
Durgesh, R.; Sreenivasulu, R.; Raju, R.R. Synthesis and anti-tumor evaluation of novel 5- bromo indole-aryl ketohydrazide-hydrazone analogues. Asian J. Chem., 2018, 30, 1201-1204.
Durgesh, R.; Sreenivasulu, R.; Raju, R.R. Synthesis and anti-tumor evaluation of Indole-substituted Indole fused keto hydrazide-hydrazones. J. Pharm. Res., 2018, 12, 42-46.
Stillings, M.R.; Welbourn, A.P.; Walter, D.S. Substituted 1,3,4-thiadiazoles with anti convulsant activity. 2-aminoalkyl derivatives. J. Med. Chem., 1986, 29, 2280-2284.
Hu, Y.; Li, C-Y.; Wang, X-M.; Yang, Y-H.; Zhu, H-L. 1,3,4-thiadiazole: Synthesis, eactions and applications in medicinal, agricultural, and materials chemistry. Chem. Rev., 2014, 114, 5572-5610.
Zhao, J.; Chen, B.Q.; Shi, Y.P.; Liu, Y.M.; Zhao, H.C.; Cheng, J. Synthesis and in vitro antitumor activity of 1,3,4-thiadiazole derivatives based on benzisoselenazolone. Chin. Chem. Lett., 2012, 23, 817-819.
Foroumadi, A.; Rineh, A.; Emami, S.; Siavoshi, F.; Massarrat, S.; Safari, F.; Rajabalian, S.; Falahati, M.; Lotfali, E.; Shafiee, A. Synthesis and anti-Helicobacter pylori activity of 5- (nitroaryl)-1,3,4-thiadiazoles with certain sulphur containing alkyl side chain. Bioorg. Med. Chem. Lett., 2008, 18, 3315-3320.
Foroumadi, A. kargar, Z.; Sakhteman, A.; Sharifzadeh, Z.; Feyzmohammadi, R.; kazemi, M.; Shafiee, A. Synthesis and antimycobacterial activity of some alkyl [5-(nitroaryl)-1,3,4- thiadiazol-2-ylthio]propionates. Bioorg. Med. Chem. Lett., 2006, 16, 1164-1167.
Yusuf, M. khan, R.A.; Ahmed, B. Syntheses and anti-depressant activity of 5-amino-1,3,4- thiadiazole-2-thiol imines and thiobenzyl derivatives. Bioorg. Med. Chem., 2008, 16, 8029-8034.
Kharb, R.; Kaur, P.; Sharma, P.C.; Shahar Yar, M. Significance of thiadiazole derivatives as antimicrobial agents. Rev. Pap., 2011, 2, 1520-1540.
Du, H.T.; Du, H.J. Synthesis and biological activity of 6-(substituted)-3-(3,4,5-trimethoxyphenyl)-1,2,4-triazolo [3,4-b][1,3,4] thiadiazole. Chin. J. Org. Chem., 2010, 30, 137-141.
Liu, F.; Luo, X.Q.; Song, B.A.; Bhadury, P.S.; Yang, S.; Jin, L.H.; Xue, W.; Hu, D.Y. Synthesis and antifungal activity of novel sulfoxide derivatives containing trimethoxy phenyl substituted 1,3,4-thiadiazole and 1,3,4-oxadiazole moiety. Bioorg. Med. Chem., 2008, 16, 3632-3640.
Schenone, S.; Brullo, C.; Bruno, O.; Bondavalli, F.; Ranise, A.; Filippelli, W.; Rinaldi, B.; Capuano, A.; Falcone, G. New 1,3,4-thiadiazole derivatives endowed with analgesic and anti-inflammatory activities. Bioorg. Med. Chem., 2006, 14, 1698-1705.
Chen, Z.; Xu, W.; Liu, K.; Yang, S.; Fan, H.; Bhadury, P.S.; Hu, D.Y.; Zhang, Y. Synthesis and antiviral activity of 5-(4-chlorophenyl)-1,3,4-thiadiazole sulphonamides. Molecules, 2010, 15, 9046-9056.
Iyer, G.; Bellantone, R.; Taft, D. In vitro characterization of the erythrocyte distribution of methazolamide: A model of erythrocyte transport and binding kinetics. J. Pharmacokinet. Biopharm., 1999, 27, 45-66.
Hall, B.S.; Wilkinson, S.R. Targeting the substrate preference of a type I nitro reductase to develop antitrypanosomal Quinone-based prodrugs. Antimicrob. Agents Chemother., 2012, 56, 115-123.
Savariz, F.C.; Formagio, A.S.N.; Barbosa, V.A.; Foglio, M.A.; Carvalho, J.E.; Duarte, M.C.T.; Filho, B.P.D.; Sarragiotto, M.H. Synthesis, antitumor and antimicrobial activity of novel 1-substituted phenyl-3-[3-alkylamino(methyl)-2-thioxo-1,3,4-oxadiazol-5-yl]β- carboline derivatives. J. Braz. Chem. Soc., 2010, 21, 288-298.
Ergun, Y.; Orhan, O.F.; Ozer, U.G.; Gisi, G. Synergistic effect of [1H- [1,2,4]oxadiazole [4,3-a]quinoxalin-1-one] and antidepressant drugs in the mouse forced swimming test. Possible involvement of serotonergic pathway. Eur. J. Pharmacol., 2010, 630, 74-78.
Temesgen, Z.; Siraj, D.S. Raltegravir: First in class HIV integrase inhibitor. Ther. Clin. Risk Manag., 2008, 4, 493-500.
Sahin, G.; Palaska, E.; Ekizoglu, M.; Ozalp, M. Synthesis and antimicrobial activity of some 1,3,4-oxadiazole derivatives. Farmaco, 2002, 57, 539-542.
Sangshetti, J.N.; Chabukswar, A.R.; Shinde, D.B. Microwave assisted one pot synthesis of some novel 2,5-disubstituted 1,3,4-oxadiazoles as antifungal agents. Bioorg. Med. Chem. Lett., 2011, 21, 444-448.
Ahsan, M.J.; Samy, J.G.; Khalilullah, H.; Nomani, M.S.; Saraswat, P.; Singh, G.R. Molecular properties prediction and synthesis of novel 1,3,4-oxadiazole analogues as potent antimicrobial and antitubercular agents. Bioorg. Med. Chem. Lett., 2011, 21, 7246-7250.
Patel, N.B.; Patel, J.C. Synthesis and antimicrobial activity of 3-(1,3,4-oxadiazol-2- yl)quinazolin-4(3H)-ones. Sci. Pharm., 2010, 78, 171-193.
Harfenist, M.; Heuser, D.J.; Joyner, C.T.; Batchelor, J.F.; White, H.L. Selective inhibitors of monoamine oxidase. 3. Structure-activity relationship of tricyclics bearing imidazoline, oxadiazole or tetrazole groups. J. Med. Chem., 1996, 39, 1857-1863.
Sriram, D.; Banerjee, D.; Yogeeswari, P. Efavirenz mannich bases: Synthesis, anti-HIV and antitubercular activities. J. Enzyme Inhib. Med. Chem., 2009, 24, 1-5.
Khan, M.T.H.; Choudhary, M.I.; Khan, K.M.; Rani, M. Atta-ur-Rahman. Structure-activity relationships of tyrosinase inhibitory combinatorial library of 2,5-disubstituted-1,3,4-oxadiazole analogues. Bioorg. Med. Chem., 2005, 13, 3385-3395.
Almasirad, A.; Tabatabai, S.A.; Faizi, M.; Kebriaeezadeh, A.; Mehrabi, N.; Dalvandi, A.; Shafiee, A. Synthesis and anticonvulsant activity of new 2-substituted-5-[2-(2- fluorophenoxy)phenyl]-1,3,4-oxadiazoles and 1,2,4-triazoles. Bioorg. Med. Chem. Lett., 2004, 14, 6057-6059.
James, N.D.; Growcott, J.W. Zibotentan. Drugs Future, 2009, 34, 624-633.

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