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Letters in Drug Design & Discovery

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

Research Article

Synthesis, Characterization, Free-radical Scavenging Capacity and Antioxidant Activity of Novel Series of Hydrazone, 1,3,4-oxadiazole and 1,2,4- triazole Derived from 3,5-dimethyl-1H-pyrazole

Author(s): Khalid Karrouchi*, Saad Fettach, Smaail Radi*, El bekkaye Yousfi, Jamal Taoufik, Yahia Nasser Mabkhot, Seham Alterary, My El Abbes Faouzi and Muhammed Ansar

Volume 16, Issue 7, 2019

Page: [712 - 720] Pages: 9

DOI: 10.2174/1570180815666180516103050

Price: $65

Abstract

Background: Pyrazole is an important class of heterocyclic compound, has been shown to exhibit diverse biological and pharmacological activities such as anti-inflammatory, anti-cancer, antioxidant, etc.

Methods: In this study, a series of novel 3,5-dimethyl-1H-pyrazole derivatives containing hydrazine 4a-l have been synthesized via the reaction of the 2-(3,5-dimethyl-1H-pyrazol-1-yl)acetohydrazide. All synthesized compounds have been tested for their in vitro antioxidant activities via utilization of 1,1-biphenyl-2-picrylhydrazyl (DPPH) as a free radical scavenging reagent.

Results: The data reported herein indicates that compound 4k showed potential radical scavenging capacity and compounds 4f and 4g exhibited best activity for the iron binding while comparing with positive controls.

Conclusion: Good activity was noted for some compounds. In particular, compound 4k showed the highest antioxidant activity with IC50 values of 22.79 ± 3.64 and 1.35 ± 0.66 μg/mL in the DPPH and ABTS tests, respectively.

Keywords: Synthesis, 3, 5-dimethyl-1H-pyrazole, 1, 3, 4-oxadiazole, 1, 2, 4-triazole, DPPH, ABTS, metal chelating activity.

Graphical Abstract

[1]
Valko, M.; Leibfritz, D.; Moncol, J.; Cronin, M.T.D.; Mazur, M.; Telser, J. Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol., 2007, 39, 44-84.
[2]
Ray, P.D.; Huang, B-W.; Tsuji, Y. Reactive oxygen species (ROS) homeostasis and redox regulation in cellular signaling. Cell. Signal., 2012, 24, 981-990.
[3]
Vertuani, S.; Angusti, A.; Manfredini, S. The antioxidants and pro-antioxidants network: An overview. Curr. Pharm. Des., 2004, 10, 1677-1694.
[4]
Kotaiah, Y.; Nagaraju, K.; Harikrishna, N.; Venkata Rao, C.; Yamini, L.; Vijjulatha, M. Synthesis, docking and evaluation of antioxidant and antimicrobial activities of novel 1,2,4-triazolo [3,4-b][1,3,4]thiadiazol-6-yl)selenopheno [2,3-d]pyrimidines. Eur. J. Med. Chem., 2014, 75, 195-202.
[5]
Rangaswamy, J.; Kumar, H.V.; Harini, S.T.; Naik, N. Functionalized 3-(benzofuran-2-yl)-5-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole scaffolds: A new class of antimicrobials and antioxidants. Arab. J. Chem., 2017, 10, S2685-S2696.
[6]
Mahajan, P.; Nikam, M.; Asrondkar, A.; Bobade, A.; Gill, C. Synthesis, antioxidant, and anti‐inflammatory evaluation of novel thiophene‐fused quinoline based β‐diketones and derivatives. J. Heterocycl. Chem., 2017, 54, 1415-1422.
[7]
Nagamallu, R.; Srinivasan, B.; Ningappa, M.B.; Kariyappa, A.K. Synthesis of novel coumarin appended bis(formylpyrazole) derivatives: Studies on their antimicrobial and antioxidant activities. Bioorg. Med. Chem. Lett., 2016, 26, 690-694.
[8]
Hernández-Vázquez, E.; Salgado-Barrera, S.; Ramírez-Espinosa, J.J.; Estrada-Soto, S.; Hernández-Luis, F. Synthesis and molecular docking of N′-arylidene-5-(4-chlorophenyl)-1-(3,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carbohydrazides as novel hypoglycemic and antioxidant dual agents. Bioorg. Med. Chem., 2016, 24, 2298-2306.
[9]
Hassan, G.S.; Abou-Seri, S.M.; Kamel, G.; Ali, M.M. Celecoxib analogs bearing benzofuran moiety as cyclooxygenase-2 inhibitors: Design, synthesis and evaluation as potential anti-inflammatory agents. Eur. J. Med. Chem., 2014, 76, 482-493.
[10]
Uslaner, J.M.; Parmentier-Batteur, S.; Flick, R.B.; Surles, N.O.; Lam, J.S.; McNaughton, C.H.; Jacobson, M.A.; Hutson, P.H. Dose-dependent effect of CDPPB, the mGluR5 positive allosteric modulator, on recognition memory is associated with GluR1 and CREB phosphorylation in the prefrontal cortex and hippocampus. Neuropharmacology, 2009, 57, 531-538.
[11]
Friedrich, G.; Rose, T.; Rissler, K. Determination of lonazolac and its hydroxy and O-sulfated metabolites by on-line sample preparation liquid chromatography with fluorescence detection. J. Chromatogr. B., 2002, 766, 295-305.
[12]
Hampp, C.; Hartzema, A.G.; Kauf, T.L. Cost-utility analysis of rimonabant in the treatment of obesity. Value Health, 2008, 11, 389-399.
[13]
Spitz, I.; Novis, B.; Ebert, R.; Trestian, S.; LeRoith, D.; Creutzfeldt, W. Betazole-induced GIP secretion is not mediated by gastric HCl. Metabolism, 1982, 31, 380-382.
[14]
Luttinger, D.; Hlasta, D.J. Antidepressant agents. Annu. Rep. Med. Chem., 1987, 22, 21-30.
[15]
Tsutomu, K.; Toshitaka, N. Effects of 1, 3-diphenyl-5-(2-dimethylaminopropionamide)-pyrazole [difenamizole] on a conditioned avoidance response. Neuropharmacology, 1978, 17, 249-256.
[16]
García-Lozano, J.; Server-Carrió, J.; Escrivà, E.; Folgado, J-V.; Molla, C.; Lezama, L. X-ray crystal structure and electronic properties of chlorobis (mepirizole) copper (II) tetrafluoroborate (mepirizole= 4-methoxy-2-(5-methoxy-3-methyl-1H-pyrazol-1-yl)-6-methylpyrimidine). Polyhedron, 1997, 16, 939-944.
[17]
Kamal, A.; Shaik, A.B.; Jain, N.; Kishor, C.; Nagabhushana, A.; Supriya, B.; Kumar, G.B.; Chourasiya, S.S.; Suresh, Y.; Mishra, R.K. Design and synthesis of pyrazole-oxindole conjugates targeting tubulin polymerization as new anticancer agents. Eur. J. Med. Chem., 2015, 92, 501-513.
[18]
Farag, A.M.; Mayhoub, A.S.; Eldebss, T.; Amr, A.G.E.; Ali, K.A.; Abdel‐Hafez, N.A.; Abdulla, M.M. Synthesis and structure‐activity relationship studies of pyrazole‐based heterocycles as antitumor agents. Arch. Pharm., 2010, 343, 384-396.
[19]
Karrouchi, K.; Chemlal, L.; Taoufik, J.; Cherrah, Y.; Radi, S.; El Abbes, F.M.; Ansar, M. Synthesis, antioxidant and analgesic activities of Schiff bases of 4-amino-1,2,4-triazole derivatives containing a pyrazole moiety. Ann. Pharm. Fr., 2016, 74, 431-438.
[20]
Chae, E.; Shin, Y-J.; Ryu, E-J.; Ji, M.K.; Ryune, C.N.; Lee, K-H.; Jeong, H.J.; Kim, S-J.; Choi, Y.; Seok, O.K.; Park, C-E.; Soo Yoon, Y. Discovery of biological evaluation of pyrazole/imidazole amides as mGlu5 receptor negative allosteric modulators. Bioorg. Med. Chem. Lett., 2013, 23, 2134-2139.
[21]
Ouyang, G.; Chen, Z.; Cai, X-J.; Song, B-A.; Bhadury, P.S.; Yang, S.; Jin, L-H.; Xue, W.; Hu, D-Y.; Zeng, S. Synthesis and antiviral activity of novel pyrazole derivatives containing oxime esters group. Bioorg. Med. Chem., 2008, 16, 9699-9707.
[22]
Vijesh, A.; Isloor, A.M.; Shetty, P.; Sundershan, S.; Fun, H.K. New pyrazole derivatives containing 1, 2, 4-triazoles and benzoxazoles as potent antimicrobial and analgesic agents. Eur. J. Med. Chem., 2013, 62, 410-415.
[23]
Niţulescu, G.M.; Păunescu, H.; Drăghici, C.; Missir, A-V.; Coman, O.A.; Fulga, I. Synthesis and pharmacological evaluation of some new pyrazole derivatives. Farmacia, 2010, 58, 190-197.
[24]
Tewari, A.K.; Singh, V.P.; Yadav, P.; Gupta, G.; Singh, A.; Goel, R.K.; Shinde, P.; Mohan, C.G. Synthesis, biological evaluation and molecular modeling study of pyrazole derivatives as selective COX-2 inhibitors and anti-inflammatory agents. Bioorg. Chem., 2014, 56, 8-15.
[25]
Fustero, S.; Román, R.; Sanz-Cervera, J.F.; Simón-Fuentes, A.; Cuñat, A.C.; Villanova, S.; Murguía, M. Improved regioselectivity in pyrazole formation through the use of fluorinated alcohols as solvents: Synthesis and biological activity of fluorinated tebufenpyrad analogs. J. Org. Chem., 2008, 73, 3523-3529.
[26]
Dai, H.; Xiao, Y-S.; Li, Z.; Xu, X-Y.; Qian, X-H. The thiazoylmethoxy modification on pyrazole oximes Synthesis and insecticidal biological evaluation beyond acaricidal activity. Chin. Chem. Lett., 2014, 25, 1014-1016.
[27]
Nagahori, H.; Yoshino, H.; Tomigahara, Y.; Isobe, N.; Kaneko, H.; Nakatsuka, I. Metabolism of furametpyr. 1. Identification of metabolites and in vitro biotransformation in rats and humans. J. Agric. Food Chem., 2000, 48, 5754-5759.
[28]
Lahm, G.P.; Cordova, D.; Barry, J.D. New and selective ryanodine receptor activators for insect control. Bioorg. Med. Chem., 2009, 17, 4127-4133.
[29]
Karrouchi, K.; Yousfi, E.; Sebbar, N.; Ramli, Y.; Taoufik, J.; Ouzidan, Y.; Ansar, M.H.; Mabkhot, Y.; Ghabbour, H.; Radi, S. New pyrazole-hydrazone derivatives: X-ray analysis, molecular structure investigation via Density Functional Theory (DFT) and their high in-situ catecholase activity. Int. J. Mol. Sci., 2017, 18, 2215.
[30]
Rollas, S.; Küçükgüzel, S.G. Biological activities of hydrazone derivatives. Molecules, 2007, 12, 1910-1939.
[31]
Hassan, G.S.; Kadry, H.H.; Abou-Seri, S.M.; Ali, M.M.; Mahmoud, A.E.E-D. Synthesis and in vitro cytotoxic activity of novel pyrazolo [3,4-d]pyrimidines and related pyrazole hydrazones toward breast adenocarcinoma MCF-7 cell line. Bioorg. Med. Chem., 2011, 19, 6808-6817.
[32]
Fan, C.; Su, H.; Zhao, J.; Zhao, B.; Zhang, S.; Miao, J. A novel copper complex of salicylaldehyde pyrazole hydrazone induces apoptosis through up-regulating integrin β4 in H322 lung carcinoma cells. Eur. J. Med. Chem., 2010, 45, 1438-1446.
[33]
Charret, K.S.; Lagrota-Cândido, J.; Carvalho-Pinto, C.E.; Hottz, C.F.; Lira, M-L.F.; Rodrigues, R.F.; Gomes, A.O.; Bernardino, A.M.; Canto-Cavalheiro, M.M.; Leon, L.L.; Amaral, V.F. The histopathological and immunological pattern of CBA mice infected with Leishmania amazonensis after treatment with pyrazole carbohydrazide derivatives. Exp. Parasitol., 2013, 133, 201-210.
[34]
Dias, L.R.S.; Salvador, R.R.S. Pyrazole carbohydrazide derivatives of pharmaceutical interest. Pharmaceuticals, 2012, 5, 317-324.
[35]
Xia, Y.; Fan, C-D.; Zhao, B-X.; Zhao, J.; Shin, D-S.; Miao, J-Y. Synthesis and structure-activity relationships of novel 1-arylmethyl-3-aryl-1H-pyrazole-5-carbohydrazide hydrazone derivatives as potential agents against A549 lung cancer cells. Eur. J. Med. Chem., 2008, 43, 2347-2353.
[36]
Şahin, D.; Bayrak, H.; Demirbaş, A.; Demirbaş, N.; Karaoğlu, Ş.A. Design and synthesis of new 1, 2, 4-triazole derivatives containing morpholine moiety as antimicrobial agents. Turk. J. Chem., 2012, 36, 411-426.
[37]
Wang, B-L.; Zhang, L-Y.; Zhan, Y-Z.; Zhang, Y.; Zhang, X.; Wang, L-Z.; Li, Z-M. Synthesis and biological activities of novel 1, 2, 4-triazole thiones and bis (1, 2, 4-triazole thiones) containing phenylpyrazole and piperazine moieties. J. Fluor. Chem., 2016, 184, 36-44.
[38]
Mohan, K.K.; Inturi, B.; Pujar, G.V.; Purohit, M.N.; Vijaykumar, G.S. Design, synthesis and 3D-QSAR studies of new diphenylamine containing 1,2,4-triazoles as potential anti-tubercular agents. Eur. J. Med. Chem., 2014, 84, 516-529.
[39]
Ünver, Y.; Sancak, K.; Çelik, F.; Birinci, E.; Küçük, M.; Soylu, S.; Burnaz, N.A. New thiophene-1,2,4-triazole-5(3)-ones: Highly bioactive thiosemicarbazides, structures of Schiff bases and triazole-thiols. Eur. J. Med. Chem., 2014, 84, 639-650.
[40]
Radwan, R.R.; Zaher, N.H.; El-Gazzar, M.G. Novel 1, 2, 4-triazole derivatives as antitumor agents against hepatocellular carcinoma. Chem. Biol. Interact., 2017, 274, 68-79.
[41]
Labanauskas, L.; Udrenaite, E.; Gaidelis, P.; Brukštus, A. Synthesis of 5-(2-,3- and 4-methoxyphenyl)-4H-1,2,4-triazole-3-thiol derivatives exhibiting anti-inflammatory activity. Farmaco, 2004, 59, 255-259.
[42]
Li, Y-D.; Mao, W-T.; Fan, Z-J.; Li, J-J.; Fang, Z.; Ji, X-T.; Hua, X-W.; Zong, G-N.; Li, F-Y.; Liu, C-L.; Yu, J-H. Synthesis and biological evaluation of novel 1,2,4-triazole containing 1,2,3-thiadiazole derivatives. Chin. Chem. Lett., 2013, 24, 1134-1136.
[43]
Raval, J.P.; Akhaja, T.N.; Jaspara, D.M.; Myangar, K.N.; Patel, N.H. Synthesis and in vitro antibacterial activity of new oxoethylthio-1,3,4-oxadiazole derivatives. J. Saudi Chem. Soc., 2014, 18, 101-106.
[44]
Rane, R.A.; Bangalore, P.; Borhade, S.D.; Khandare, P.K. Synthesis and evaluation of novel 4-nitropyrrole-based 1, 3, 4-oxadiazole derivatives as antimicrobial and anti-tubercular agents. Eur. J. Med. Chem., 2013, 70, 49-58.
[45]
Zhang, S.; Luo, Y.; He, L-Q.; Liu, Z-J.; Jiang, A-Q.; Yang, Y-H.; Zhu, H-L. Synthesis, biological evaluation, and molecular docking studies of novel 1,3,4-oxadiazole derivatives possessing benzotriazole moiety as FAK inhibitors with anticancer activity. Bioorg. Med. Chem., 2013, 21, 3723-3729.
[46]
Biju, C.R.; Ilango, K.; Prathap, M.; Rekha, K. Design and microwave-assisted synthesis of 1,3,4-oxadiazole derivatives for analgesie and anti-inflammatory activity. Young Pharm, 2012, 4, 33-37.
[47]
Li, T.; Li, S.; Dong, Y.; Zhu, R.; Liu, Y. Antioxidant activity of penta-oligogalacturonide, isolated from haw pectin, suppresses triglyceride synthesis in mice fed with a high-fat diet. Food Chem., 2014, 145, 335-341.
[48]
Himmi, B.; Douche, D.; El Louzi, A.; Karrouchi, K. Synthesis and in vitro antioxidant activity of some 8-hydoxyquinoline derivatives. J. Chem. Pharm. Res., 2016, 8, 525-528.
[49]
Re, R.; Pellegrini, N.; Proteggente, A.; Pannala, A.; Yang, M.; Rice-Evans, C. Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic. Biol. Med., 1999, 26, 1231-1237.
[50]
Aktas-Yokus, O.; Yuksek, H.; Gursoy-Kol, O.; Alpay-Karaoglu, S. Synthesis and biological evaluation of new 1, 2, 4-triazole derivatives with their potentiometric titrations. Med. Chem. Res., 2015, 24, 2813-2824.
[51]
Rival, S.G.; Boeriu, C.G.; Wichers, H.J. Caseins and casein hydrolysates antioxidative properties and relevance to lipoxygenase inhibition. J. Agric. Food Chem., 2001, 49, 295-302.
[52]
Finefrock, A.E.; Bush, A.I.; Doraiswamy, P.M. Current status of metals as therapeutic targets in Alzheimer’s disease. J. Am. Geriatr. Soc., 2003, 51, 1143-1148.
[53]
Leong, L.; Shui, G. An investigation of antioxidant capacity of fruits in Singapore markets. Food Chem., 2002, 76, 69-75.
[54]
Gordon, M.H. The Mechanism of Antioxidant Action in Vitro. In: Hudson B.J.F. (eds) Food Antioxidants. Elsevier Applied Food Science Series. Springer, Dordrecht. 1990.

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