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Letters in Drug Design & Discovery

Author(s): Rafaila Rafique, Arshia, Kanwal, Khalid Mohammed Khan*, Sridevi Chigurupati, Uzma Salar, Muhammad Taha and Shahnaz Perveen

DOI: 10.2174/1570180817999200424074455

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Discovery of New N-hydrazinecarbothioamide Indazole Hybrids: As Potential Radical (ABTS and DPPH) Scavengers

Page: [1177 - 1185] Pages: 9

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Abstract

Background: Free radicals are the main cause of numerous diseases. Their overproduction needs to be controlled in order to combat several ailments. The current study deals with the discovery of new free radical scavengers.

Methods: Substituted N-hydrazinecarbothioamide indazoles 1-18 were evaluated for DPPH and ABTS radical scavenging activities.

Results and Discussions: All synthetic compounds possess good radical DPPH and ABTS scavenging potential in the ranges of IC50 = 2.11 ± 0.17 - 5.3 ± 0.11 μM and IC50 = 2.31 ± 0.06 - 5.5 ± 0.07 μM, respectively, as compared to standard ascorbic acid having IC50 = 2.02 ± 0.11 μM for DPPH and IC50 = 2.1 ± 0.07 μM for ABTS.

Conclusion: These compounds could serve as leads for antioxidant activity that have the ability to control free radical generation and ward off free radical-induced disorders.

Keywords: Indazole, carbothioamide, antioxidant, radical scavengers, DPPH, ABTS.

Graphical Abstract

[1]
Denya, I.; Malan, S.F.; Joubert, J. Indazole derivatives and their therapeutic applications: A patent review (2013-2017). Expert Opin. Ther. Pat., 2018, 28(6), 441-453.
[http://dx.doi.org/10.1080/13543776.2018.1472240] [PMID: 29718740]
[2]
Shrivastava, A.; Chakraborty, A.; Upmanyu, N. Recent rogress in chemistry and biology of indazole and its derivatives: A brief review. Austin J. Anal. Pharm. Chem., 2016, 3, 1076.
[3]
Büchel, G.E.; Stepanenko, I.N.; Hejl, M.; Jakupec, M.A.; Keppler, B.K.; Heffeter, P.; Berger, W.; Arion, V.B. Osmium(IV) complexes with 1H- and 2H-indazoles: tautomer identity versus spectroscopic properties and antiproliferative activity. J. Inorg. Biochem., 2012, 113, 47-54.
[http://dx.doi.org/10.1016/j.jinorgbio.2012.04.001] [PMID: 22687494]
[4]
Gaikwad, D.D.; Chapolikar, A.D.; Devkate, C.G.; Warad, K.D.; Tayade, A.P.; Pawar, R.P.; Domb, A.J. Synthesis of indazole motifs and their medicinal importance: An overview. Eur. J. Med. Chem., 2015, 90, 707-731.
[http://dx.doi.org/10.1016/j.ejmech.2014.11.029] [PMID: 25506810]
[5]
Rafique, R.; Saad, S.M.; Khan, K.M.; Perveen, S.; Taha, M. Facile CuCl2. 2H2O catalyzed one-pot conversion of dimedone into highly functionalized indazole based N-arylhydrazinecarbothioamides. J. Saudi Chem. Soc., 2019, 23, 92-97.
[6]
Ali, N.A.; Dar, B.A.; Pradhan, V.; Farooqui, M.; Farooqui, M. Chemistry and biology of indoles and indazoles: A mini-review. Mini Rev. Med. Chem., 2013, 13(12), 1792-1800.
[http://dx.doi.org/10.2174/1389557511313120009] [PMID: 22625410]
[7]
Chandrasekhar, T.; Reddy, A.B.; Kumar, L.V.; Naik, P.J. Synthesis and biological evaluation of some new indazole-3-carboxamide derivatives. Pharma Chem., 2012, 4.
[8]
Chevalier, A.; Ouahrouch, A.; Arnaud, A.; Gallavardin, T.; Franck, X. An optimized procedure for direct access to 1H-indazole-3-carboxaldehyde derivatives by nitrosation of indoles. RSC Advances, 2018, 8, 13121-13128.
[http://dx.doi.org/10.1039/C8RA01546E]
[9]
Vidyacharan, S.; Adhikari, C.; Krishna, V.S.; Reshma, R.S.; Sriram, D.; Sharada, D.S. A robust synthesis of functionalized 2H-indazoles via solid state melt reaction (SSMR) and their anti-tubercular activity. Bioorg. Med. Chem. Lett., 2017, 27(7), 1593-1597.
[http://dx.doi.org/10.1016/j.bmcl.2017.02.021] [PMID: 28254485]
[10]
Lian, Y.; Bergman, R.G.; Lavis, L.D.; Ellman, J.A. Rhodium(III)-catalyzed indazole synthesis by C-H bond functionalization and cyclative capture. J. Am. Chem. Soc., 2013, 135(19), 7122-7125.
[http://dx.doi.org/10.1021/ja402761p] [PMID: 23642256]
[11]
Khan, K.M.; Karim, A.; Saied, S.; Ambreen, N.; Saleem, M.; Amyn, A.; Perveen, S.; Ahmad, A.; Choudhary, M.I. Synthesis, antioxidant and carbonic anhydrase inhibitory potential of Schiff bases of thiazoles. J. Pharm. Res., 2012, 5, 661-663.
[12]
Lobo, V.; Patil, A.; Phatak, A.; Chandra, N. Free radicals, antioxidants and functional foods: Impact on human health. Pharmacogn. Rev., 2010, 4(8), 118-126.
[http://dx.doi.org/10.4103/0973-7847.70902] [PMID: 22228951]
[13]
Olszowy, M.; Dawidowicz, A.L. Is it possible to use the DPPH and ABTS methods for reliable estimation of antioxidant power of colored compounds? Chem. Pap., 2018, 72, 393-400.
[http://dx.doi.org/10.1007/s11696-017-0288-3]
[14]
Aziz, A.N.; Taha, M.; Ismail, N.H.; Anouar, H.; Yousuf, S.; Jamil, W.; Awang, K.; Ahmat, N.; Khan, K.M.; Kashif, S.M. Synthesis, crystal structure, DFT studies and evaluation of the antioxidant activity of 3,4-dimethoxybenzenamine Schiff bases. Molecules, 2014, 19(6), 8414-8433.
[http://dx.doi.org/10.3390/molecules19068414] [PMID: 24950444]
[15]
Vallyathan, V.; Shi, X. The role of oxygen free radicals in occupational and environmental lung diseases. Environ. Health Perspect., 1997, 105(Suppl. 1), 165-177.
[PMID: 9114285]
[16]
Uttara, B.; Singh, A.V.; Zamboni, P.; Mahajan, R.T. Oxidative stress and neurodegenerative diseases: A review of upstream and downstream antioxidant therapeutic options. Curr. Neuropharmacol., 2009, 7(1), 65-74.
[http://dx.doi.org/10.2174/157015909787602823] [PMID: 19721819]
[17]
Phaniendra, A.; Jestadi, D.B.; Periyasamy, L. Free radicals: properties, sources, targets, and their implication in various diseases. Indian J. Clin. Biochem., 2015, 30(1), 11-26.
[http://dx.doi.org/10.1007/s12291-014-0446-0] [PMID: 25646037]
[18]
Zhang, B.; Deng, Z.; Ramdath, D.D.; Tang, Y.; Chen, P.X.; Liu, R.; Liu, Q.; Tsao, R. Phenolic profiles of 20 Canadian lentil cultivars and their contribution to antioxidant activity and inhibitory effects on α-glucosidase and pancreatic lipase. Food Chem., 2015, 172, 862-872.
[http://dx.doi.org/10.1016/j.foodchem.2014.09.144] [PMID: 25442631]
[19]
Halliwell, B. How to characterize a biological antioxidant. Free Radic. Res. Commun., 1990, 9(1), 1-32.
[http://dx.doi.org/10.3109/10715769009148569] [PMID: 2159941]
[20]
Nicklisch, S.C.; Waite, J.H. Optimized DPPH assay in a detergent-based buffer system for measuring antioxidant activity of proteins. MethodsX, 2014, 1, 233-238.
[http://dx.doi.org/10.1016/j.mex.2014.10.004] [PMID: 25530949]
[21]
Wu, C.H.; Yeh, C.T.; Yen, G.C. Epigallocatechin gallate (EGCG) binds to low-density lipoproteins (LDL) and protects them from oxidation and glycation under high-glucose conditions mimicking diabetes. Food Chem., 2010, 121, 639-644.
[http://dx.doi.org/10.1016/j.foodchem.2010.02.008]
[22]
Thaipong, K.; Boonprakoba, U.; Crosbyb, K.; Zevallosc, L.C.; Byrne, D.H. Comparison of ABTS, DPPH, FRAP, and ORAC assays for estimating antioxidant activity from guava fruit extracts. J. Food Compos. Anal., 2006, 19, 669-675.
[http://dx.doi.org/10.1016/j.jfca.2006.01.003]
[23]
Ahad, G.; Khan, M.; Khan, A.; Ibrahim, M.; Salar, U. Kanwal, Khan.K.M; Perveen, S. Synthesis, structural characterization, and antioxidant activities of 2,4-dinitrophenyl-hydrazone derivatives. J. Chem. Soc. Pak., 2018, 40, 961-961.
[24]
Khan, K.M.; Khan, M.; Ambreen, N.; Rahim, F.; Muhammad, B.; Ali, S.; Haider, S.M.; Perveen, S.; Choudhary, M.I. Bis-Schiff bases of isatins: A new class of antioxidant. J. Pharm. Res., 2011, 4, 3402-3404.
[25]
Khan, K.M.; Rani, M.; Ambreen, N.; Ejaza, A.; Perveen, S.; Haider, S.M.; Choudhary, M.I.; Voelter, W. Acyl hydrazides: Potent antioxidants. Lett. Drug Des. Discov., 2012, 9, 135-139.
[http://dx.doi.org/10.2174/157018012799079798]
[26]
Khan, K.M.; Mughal, U.R.; Omar, I.; Choudhary, M.I. Microwaves-assisted syntheses of imidazolylbenzamides and their antioxidant activities. Lett. Drug Des. Discov., 2008, 5, 152-157.
[http://dx.doi.org/10.2174/157018008784083974]
[27]
Khan, K.M.; Khan, A.; Taha, M.; Salar, U.; Hameed, A.; Ismail, N.H.; Jamil, W.; Saad, S.M.; Perveen, S.; Kashif, S.M. Synthesis of 4-amino-1,5-dimethyl-2-phenylpyrazolone derivatives and their antioxidant activity. J. Chem. Soc. Pak., 2015, 37, 802-810.
[28]
Khan, K.M.; Rahim, F.; Khan, A.; Ali, S.; Taha, M.; Saad, S.M.; Khan, M.; Najeebullah, S.A.; Perveen, S.; Choudhary, M.I. Synthesis of benzophenone hydrazone analogs and their DPPH radical scavenging and urease inhibitory activities. J. Chem. Soc. Pak., 2015, 37, 479-483.
[29]
Thadhani, V.M.; Choudhary, M.I.; Ali, S.; Omar, I.; Siddique, H.; Karunaratne, V. Antioxidant activity of some lichen metabolites. Nat. Prod. Res., 2011, 25(19), 1827-1837.
[http://dx.doi.org/10.1080/14786419.2010.529546] [PMID: 22136374]
[30]
Chigurupati, S.; Selvaraj, M.; Mani, V.; Selvarajan, K.K.; Mohammad, J.I.; Kaveti, B.; Bera, H.; Palanimuthu, V.R.; Teh, L.K.; Salleh, M.Z. Identification of novel acetylcholinesterase inhibitors: Indolopyrazoline derivatives and molecular docking studies. Bioorg. Chem., 2016, 67, 9-17.
[http://dx.doi.org/10.1016/j.bioorg.2016.05.002] [PMID: 27231830]
[31]
Rafique, R.; Khan, K.M. Arshia; Kanwal; Chigurupati, S.; Wadood, A.; Rehman, A.U.; Karunanidhi, A.; Hameed, S.; Taha, M.; Al-Rashida, M. Synthesis of new indazole based dual inhibitors of α-glucosidase and α-amylase enzymes, their in vitro, in silico and kinetics studies. Bioorg. Chem., 2020., 94103195
[http://dx.doi.org/10.1016/j.bioorg.2019.103195] [PMID: 31451297]
[32]
Chen, X.; Kitts, D.D.; Ji, D.; Ding, J. Free radical scavenging activities of phytochemical mixtures and aqueous methanolic extracts recovered from processed coffee leaves. Int. J. Food Sci. Technol., 2019, 54, 2872-2879.
[http://dx.doi.org/10.1111/ijfs.14099]
[33]
Ruch, R.J.; Cheng, S.J.; Klaunig, J.E. Prevention of cytotoxicity and inhibition of intercellular communication by antioxidant catechins isolated from Chinese green tea. Carcinogenesis, 1989, 10(6), 1003-1008.
[http://dx.doi.org/10.1093/carcin/10.6.1003] [PMID: 2470525]
[34]
Valko, M.; Leibfritz, D.; Moncol, J.; Cronin, M.T.; Mazur, M.; Telser, J. Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol., 2007, 39(1), 44-84.
[http://dx.doi.org/10.1016/j.biocel.2006.07.001] [PMID: 16978905]
[35]
Bagchi, K.; Puri, S. Free radicals and antioxidants in health and disease. EMHJ, 1998, 4, 350-360.
[36]
Vertuani, S.; Angusti, A.; Manfredini, S. The antioxidants and pro-antioxidants network: An overview. Curr. Pharm. Des., 2004, 10(14), 1677-1694.
[http://dx.doi.org/10.2174/1381612043384655] [PMID: 15134565]
[37]
Hoffman, F. Antioxidant vitamins newsletter. Nutr. Rev., 1997, 14, 234-236.
[38]
Rafique, R.; Khan, K.M. Arshia; Chigurupati, S.; Wadood, A.; Rehman, A.U.; Salar, U.; Venugopal, V.; Shamim, S.; Taha, M.; Perveen, S. Synthesis, in vitro α-amylase inhibitory, and radicals (DPPH & ABTS) scavenging potentials of new N-sulfonohydrazide substituted indazoles. Bioorg. Chem., 2020, 94, 103410
[http://dx.doi.org/10.1016/j.bioorg.2019.103410] [PMID: 31732193]
[39]
Alım, Z.; Kılıç, D.; Demir, Y. Some indazoles reduced the activity of human serum paraoxonase 1, an antioxidant enzyme: in vitro inhibition and molecular modeling studies. Arch. Physiol. Biochem., 2019, 125(5), 387-395.
[http://dx.doi.org/10.1080/13813455.2018.1470646] [PMID: 29741961]
[40]
Polo, E.; Trilleras, J.; Ramos, J.; Galdámez, A.; Quiroga, J.; Gutierrez, M. Efficient MW-assisted synthesis, spectroscopic characterization, x-ray and antioxidant properties of indazole derivatives. Molecules, 2016, 21(7), 21.
[http://dx.doi.org/10.3390/molecules21070903] [PMID: 27409599]
[41]
Sapnakumari, M.; Narayana, B.; Sarojini, B.K.; Madhu, L.N. Synthesis of new indazole derivatives as potential antioxidant agents. Med. Chem. Res., 2014, 23, 2368-2376.
[http://dx.doi.org/10.1007/s00044-013-0835-6]