Abstract
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
[5]
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.
[6]
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.
[7]
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.
[8]
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.
[9]
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.
[10]
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.
[11]
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.
[12]
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.
[13]
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.
[14]
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.
[15]
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.
[16]
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.
[17]
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.
[18]
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.
[19]
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.
[20]
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.
[21]
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.
[22]
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.
[23]
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.
[24]
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.
[25]
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.
[26]
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.
[27]
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.
[28]
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.
[29]
Kharb, R.; Kaur, P.; Sharma, P.C.; Shahar Yar, M. Significance of thiadiazole derivatives as antimicrobial agents. Rev. Pap., 2011, 2, 1520-1540.
[30]
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.
[31]
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.
[32]
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.
[33]
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.
[34]
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.
[35]
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.
[36]
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.
[38]
Temesgen, Z.; Siraj, D.S. Raltegravir: First in class HIV integrase inhibitor. Ther. Clin. Risk Manag., 2008, 4, 493-500.
[39]
Sahin, G.; Palaska, E.; Ekizoglu, M.; Ozalp, M. Synthesis and antimicrobial activity of some 1,3,4-oxadiazole derivatives. Farmaco, 2002, 57, 539-542.
[40]
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.
[41]
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.
[42]
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.
[43]
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.
[44]
Sriram, D.; Banerjee, D.; Yogeeswari, P. Efavirenz mannich bases: Synthesis, anti-HIV and antitubercular activities. J. Enzyme Inhib. Med. Chem., 2009, 24, 1-5.
[45]
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.
[46]
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.
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