Login Register Cart 0
Generic placeholder image

Letters in Organic Chemistry

Editor-in-Chief

ISSN (Print): 1570-1786
ISSN (Online): 1875-6255

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Research Article

Synthesis and Molecular Docking Studies of Novel Triazole Derivatives as Antioxidant Agents

Author(s): Musa Özil*, Güven Tacal, Nimet Baltaş and Mustafa Emirik

Volume 17, Issue 4, 2020

Page: [309 - 320] Pages: 12

DOI: 10.2174/1570178616666190828200207

Price: $65

Abstract

A series of 1,2,4-triazole and 1,2,4- thiadiazole derivatives were prepared starting from ethyl 4-(3-methyl-5-oxo-1,5-dihydro-4H-1,2,4-triazol-4-yl)benzoate. Firstly, both ethyl ester groups were simultaneously transformed into hydrazide groups, then into thiosemicarbazide groups using both microwave- assisted and conventional methods. The latter products were interacted with NaOH and H2SO4 to form ring assemblies containing two 1,2,4-triazole and 1,3,4-thiadiazole fragments, respectively. Antioxidant activities of the synthesized compounds were determined with CUPRAC, ABTS, and DPPH assays. Most of the compounds showed significant antioxidant activity and especially, compound 3 exhibited very good SC50 value for DPPH method and compound 3, 4a, 5a exhibited very high scavenging activity to the ABTS method. In addition, the in silico analysis was carried out with the synthesized derivatives to understand the mode of interaction with superoxide dismutase (SOD) and human tyrosine kinase using docking protocols in order to find out the most active antioxidant drug having high inhibitory activity in cancer.

Keywords: Triazole, thiadiazole, docking, antioxidant, anticancer, microwave synthesis.

« Previous Next »
Graphical Abstract

[1]
Han, Z.; Hao, X.; Ma, B.; Zhu, C. Eur. J. Med. Chem., 2016, 121, 308-317.
[http://dx.doi.org/10.1016/j.ejmech.2016.05.036] [PMID: 27267001]
[2]
Banerjee, A.G.; Das, N.; Shengule, S.A.; Sharma, P.A.; Srivastava, R.S.; Shrivastava, S.K. Bioorg. Chem., 2016, 69, 102-120.
[http://dx.doi.org/10.1016/j.bioorg.2016.10.003] [PMID: 27750057]
[3]
Li, W.J.; Li, Q.; Liu, D.L.; Ding, M.W. J. Agric. Food Chem., 2013, 61(7), 1419-1426.
[http://dx.doi.org/10.1021/jf305355u] [PMID: 23350742]
[4]
Plech, T.; Kaproń, B.; Paneth, A.; Kosikowska, U.; Malm, A.; Strzelczyk, A.; Stączek, P.; Świątek, Ł.; Rajtar, B.; Polz-Dacewicz, M. Eur. J. Med. Chem., 2015, 97, 94-103.
[http://dx.doi.org/10.1016/j.ejmech.2015.04.058] [PMID: 25951434]
[5]
Al-Soud, Y.A.; Al-Dweri, M.N.; Al-Masoudi, N.A. Farmaco, 2004, 59(10), 775-783.
[http://dx.doi.org/10.1016/j.farmac.2004.05.006] [PMID: 15474054]
[6]
Kulabaş, N.; Tatar, E.; Bingöl Özakpınar, Ö.; Özsavcı, D.; Pannecouque, C.; De Clercq, E.; Küçükgüzel, İ. Eur. J. Med. Chem., 2016, 121, 58-70.
[http://dx.doi.org/10.1016/j.ejmech.2016.05.017] [PMID: 27214512]
[7]
Nagaradja, E.; Bentabed-Ababsa, G.; Scalabrini, M.; Chevallier, F.; Philippot, S.; Fontanay, S.; Duval, R.E.; Halauko, Y.S.; Ivashkevich, O.A.; Matulis, V.E.; Roisnel, T.; Mongin, F. Bioorg. Med. Chem., 2015, 23(19), 6355-6363.
[http://dx.doi.org/10.1016/j.bmc.2015.08.031] [PMID: 26344592]
[8]
Kahveci, B.; Özil, M.; Menteşe, E.; Bekircan, O.; Buruk, K. Russ. J. Org. Chem., 2008, 44, 1816-1820.
[http://dx.doi.org/10.1134/S1070428008120178]
[9]
Sarigol, D.; Uzgoren-Baran, A.; Tel, B.C.; Somuncuoglu, E.I.; Kazkayasi, I.; Ozadali-Sari, K.; Unsal-Tan, O.; Okay, G.; Ertan, M.; Tozkoparan, B. Bioorg. Med. Chem., 2015, 23(10), 2518-2528.
[http://dx.doi.org/10.1016/j.bmc.2015.03.049] [PMID: 25868745]
[10]
Walczak, K.; Gondela, A.; Suwiński, J. Eur. J. Med. Chem., 2004, 39(10), 849-853.
[http://dx.doi.org/10.1016/j.ejmech.2004.06.014] [PMID: 15464618]
[11]
Zhang, W.; Sui, G.; Li, Y.; Fang, M.; Yang, X.; Ma, X.; Zhou, W. Chem. Pharm. Bull. (Tokyo), 2016, 64(6), 616-624.
[http://dx.doi.org/10.1248/cpb.c16-00056] [PMID: 27250796]
[12]
Upadhayaya, R.S.; Sinha, N.; Jain, S.; Kishore, N.; Chandra, R.; Arora, S.K. Bioorg. Med. Chem., 2004, 12(9), 2225-2238.
[http://dx.doi.org/10.1016/j.bmc.2004.02.014] [PMID: 15080922]
[13]
Kaur, N. Synth. Commun., 2015, 45, 432-457.
[http://dx.doi.org/10.1080/00397911.2013.824982]
[14]
Kappe, C.O. Angew. Chemie-International, 2004, 43, 6250-6284.
[15]
Özil, M.; Canpolat, M. Polyhedron, 2013, 51, 82-89.
[http://dx.doi.org/10.1016/j.poly.2012.12.016]
[16]
Özil, M.; Bodur, O.; Ülker, S.; Kahveci, B. Chem. Heterocycl. Compd., 2015, 51, 88-96.
[http://dx.doi.org/10.1007/s10593-015-1664-y]
[17]
Kahveci, B.; Menteşe, E.; Özil, M.; Ülker, S.; Ertürk, M. Monatsh. Chem., 2013, 144, 993-1001.
[http://dx.doi.org/10.1007/s00706-012-0916-0]
[18]
Dayem, A.A.; Choi, H.Y.; Kim, J.H.; Cho, S-G. Cancers (Basel), 2010, 2(2), 859-884.
[http://dx.doi.org/10.3390/cancers2020859] [PMID: 24281098]
[19]
Gey, K.F. J. Nutr. Biochem., 1995, 6, 206-236.
[http://dx.doi.org/10.1016/0955-2863(95)00032-U]
[20]
Sies, H. Exp. Physiol., 1997, 82(2), 291-295.
[http://dx.doi.org/10.1113/expphysiol.1997.sp004024] [PMID: 9129943]
[21]
Halliwell, B. Annu. Rev. Nutr., 1996, 16, 33-50.
[http://dx.doi.org/10.1146/annurev.nu.16.070196.000341] [PMID: 8839918]
[22]
Özil, M.; Parlak, C.; Baltaş, N. Bioorg. Chem., 2018, 76, 468-477.
[http://dx.doi.org/10.1016/j.bioorg.2017.12.019] [PMID: 29287256]
[23]
Menteşe, E.; Ülker, S.; Kahveci, B. Chem. Heterocycl. Compd., 2015, 50, 1671-1682.
[http://dx.doi.org/10.1007/s10593-015-1637-1]
[24]
Apak, R.; Güçlü, K.; Ozyürek, M.; Karademir, S.E. J. Agric. Food Chem., 2004, 52(26), 7970-7981.
[http://dx.doi.org/10.1021/jf048741x] [PMID: 15612784]
[25]
Mentese, E.; Yilmaz, F.; Baltas, N.; Bekircan, O.; Kahveci, B. J. Enzyme Inhib. Med. Chem., 2014, 6366, 1-7.
[26]
Can, Z.; Dincer, B.; Sahin, H.; Baltas, N.; Yildiz, O.; Kolayli, S. J. Enzyme Inhib. Med. Chem., 2014, 29(6), 829-835.
[http://dx.doi.org/10.3109/14756366.2013.858144] [PMID: 24246090]
[27]
Ünver, Y.; Sancak, K.; Çelik, F.; Birinci, E.; Küçük, M.; Soylu, S.; Burnaz, N.A. Eur. J. Med. Chem., 2014, 84, 639-650.
[http://dx.doi.org/10.1016/j.ejmech.2014.01.014] [PMID: 25063946]
[28]
Menteşe, E.; Karaali, N.; Yilmaz, F.; Ulker, S.; Kahveci, B. Arch. Pharm. (Weinheim), 2013, 346(7), 556-561.
[http://dx.doi.org/10.1002/ardp.201300050] [PMID: 23737125]
[29]
Usta, A.; Yılmaz, F.; Kapucu, G.; Baltaş, N.; Menteşe, E. Lett. Org. Chem., 2015, 12, 227-232.
[http://dx.doi.org/10.2174/1570178612666150203233804]
[30]
Esteves, M.; Siquet, C.; Gaspar, A.; Rio, V.; Sousa, J.B.; Reis, S.; Marques, M.P.M.; Borges, F. Arch. Pharm. (Weinheim), 2008, 341(3), 164-173.
[http://dx.doi.org/10.1002/ardp.200700168] [PMID: 18275037]
[31]
Covacci, V.; Torsello, A.; Palozza, P.; Sgambato, A.; Romano, G.; Boninsegna, A.; Cittadini, A.; Wolf, F.I. Chem. Res. Toxicol., 2001, 14(11), 1492-1497.
[http://dx.doi.org/10.1021/tx010021m] [PMID: 11712906]
[32]
Bast, A.; Haenen, G.R.M.M.; Bruynzeel, A.M.E.; Van der Vijgh, W.J.F. Cardiovasc. Toxicol., 2007, 7(2), 154-159.
[http://dx.doi.org/10.1007/s12012-007-0018-0] [PMID: 17652822]
[33]
Brand-Williams, W.; Cuvelier, M.E.; Berset, C. Lebensm. Wiss. Technol., 1995, 28, 25-30.
[http://dx.doi.org/10.1016/S0023-6438(95)80008-5]
[34]
Small-Molecule, D.D.S. 2015-3: Schrödinger Suite 2015-3 Induced Fit Docking protocol; Glide version 6.8, Schrödinger, LLC, New York, NY, 2015; Prime version 4.1; Schrödinger, LLC: New York, NY, 2015.
[35]
Frisch, M.J.; Trucks, G.W.; Schlegel, H.B.; Scuseria, G.E.; Robb, M.A.; Cheeseman, J.R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G.A.; Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H.P.; Izmaylov, A.F.; Bloino, J.; Zheng, G.; Sonnenberg, J.L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven, T.; Montgomery, J.A.; Peralta, J.E.; Ogliaro, F.; Bearpark, M.J.; Heyd, J.; Brothers, E.N.; Kudin, K.N.; Staroverov, V.N.; Kobayashi, R.; Normand, J.; Raghavachari, K.; Rendell, A.P.; Burant, J.C.; Iyengar, S.S.; Tomasi, J.; Cossi, M.; Rega, N.; Millam, N.J.; Klene, M.; Knox, J.E.; Cross, J.B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R.E.; Yazyev, O.; Austin, A.J.; Cammi, R.; Pomelli, C.; Ochterski, J.W.; Martin, R.L.; Morokuma, K.; Zakrzewski, V.G.; Voth, G.A.; Salvador, P.; Dannenberg, J.J.; Dapprich, S.; Daniels, A.D.; Farkas, Ö.; Foresman, J.B.; Ortiz, J.V.; Cioslowski, J.; Fox, D.J. Gaussian 09, Inc., Wallingford CT, 2009.
[36]
Sherman, W.; Beard, H.S.; Farid, R. Chem. Biol. Drug Des., 2006, 67(1), 83-84.
[http://dx.doi.org/10.1111/j.1747-0285.2005.00327.x] [PMID: 16492153]

Rights & Permissions Print Cite
Article Metrics
14
© 2024 Bentham Science Publishers | Privacy Policy