SYNTHESIS, COMPLETE ASSIGNMENT OF 1H- AND 13C-NMR SPECTRA AND ANTIOXIDANT ACTIVITY OF NEW AZINE DERIVATIVE BEARING COUMARIN MOIETY
Abstract
In this research, the synthesis of a new azine derivative with coumarin moiety was performed in three reaction steps, starting from 4-hydroxycoumarin. The first step in synthesis was the acetylation of 4-hydroxycoumarin to yield 3-acetyl-4-hydroxycoumarin and then the obtained 3-acetyl-4-hydroxycoumarin was reacted with hydrazine hydrate and give a corresponding hydrazone. Condensation of the hydrazone with 4-ethoxy-3-methoxybenzaldehyde afforded the target compound 1-[1-(4-hydroxy-2-oxo-2H-chromen-3-yl)-ethylidene]-2-(4-etoxy-3-methoxybenzylidene)-hydrazine in a good yield. The resulting azine derivative is fully spectrally characterized, including complete assignment of 1H- and 13C-NMR spectra, as well as 2D NMR (1H-1H COSY, NOESY, HSQC and HMBC) spectra. The antioxidant activity of corresponding hydrazone and target compound was evaluated by DPPH method where hydrazone derivative displayed a significant and target azine good antioxidant activity, with IC50 (μM) values 11.69 and 216.60, respectively.
References
Abdel Latif, N. A., Batran, R. Z., Khedr, M. A. & Abdalla, M. M. 2016. 3-Substituted-4-hydroxycoumarin as a new scaffold with potent CDK inhibition and promising anticancer effect: Synthesis, molecular modeling and QSAR studies. Bioorganic Chemistry, 67, pp. 116-129. doi: 10.1016/j.bioorg.2016.06.005
Al-Haiza, M. A., Mostafa, M. S. & El-Kady, M. Y. 2003. Synthesis and biological evaluation of some new coumarin derivatives. Molecules, 8(2), pp. 275-286. doi: 10.3390/80200275
Chourasiya, S. S., Kathuria, D., Singh, S., Sonawane, V. C., Chakraborti, A. K. & Bharatam P. V. 2015. Design, synthesis and biological evaluation of novel unsymmetrical azines as quorum sensing inhibitors. RSC Advances, 5(97), pp. 80027-80038. doi: 10.1039/C5RA12925G
Chourasiya, S. S., Kathuria, D., Wani, A. A. & Bharatam, P. V. 2019. Azines: synthesis, structure, electronic structure and their applications. Organic & Biomolecular Chemistry, 17(37), pp. 8486-8521. doi: 10.1039/C9OB01272A
Dekić, V., Radulović, N., Vukićević, R., Dekić, B., Skropeta, D. & Palić, R. 2010. Complete assignment of the 1H and 13C NMR spectra of antimicrobial 4-arylamino-3-nitrocoumarin derivatives. Magnetic Resonance in Chemistry, 48(11), pp. 896-902. doi: 10.1002/mrc.2681
Fayed, E. A., Sabour, R., Harras, M. F. & Mehany, A. B. 2019. Design, synthesis, biological evaluation and molecular modeling of new coumarin derivatives as potent anticancer agents. Medicinal Chemistry Research, 28, pp. 1284-1297. doi: 10.1007/s00044-019-02373-x
Forezi, L. da S. M., Borba-Santos, L. P., Cardoso, M., Ferreira, V. F., Rozental, S. & Silva, de C da, F. 2018. Synthesis and Antifungal Activity of Coumarins Derivatives Against Sporothrix spp. Current Topics in Medicinal Chemistry, 18(2), pp. 164–171. doi: 10.2174/156802661866618022111550
Guerra, F. S., Araújo, R. S., Sousa, J. P., Pereira, F. D., Mendonça-Junior, F. J., Barbosa-Filho, J. & Lima, E. D. 2015. Evaluation of Antifungal Activity and Mode of Action of New Coumarin Derivative, 7-Hydroxy-6-nitro-2H-1-benzopyran-2-one, against Aspergillus spp. Evidence-based Complementary and Alternative Medicine, 2015, ID 925096. doi: 10.1155/2015/925096
Gul, H. I., Calis, U. & Vepsalainen J. 2004. Synthesis of some mono-Mannich bases and corresponding azine derivatives and evaluation of their anticonvulsant activity. Arzneimittelforschung, 54(7), pp. 359-364. doi: 10.1055/s-0031-1296984
Kadhum, A. A., Al-Amiery, A. A., Musa, A. Y. & Mohamad, A. B. 2011. The antioxidant activity of new coumarin derivatives. International Journal of Molecular Sciences, 12(9), pp. 5747-5761. doi: 10.3390/ijms12095747
Kirkiacharian, S., Thuy, D. T., Sicsic, S., Bakhchinian, R., Kurkjian, R. & Tonnaire, T. 2002. Structure-activity relationships of some 3-substituted-4-hydroxycoumarins as HIV-1 protease inhibitors. Il Farmaco, 57(9), pp. 703-708. doi: 10.1016/s0014-827x(02)01264-8
Kontogiorgis, C. A. & Hadjipavlou-Litina, D. J. 2005. Synthesis and antiinflammatory activity of coumarin derivatives. Journal of Medicinal Chemistry, 48(20), pp. 6400-6408. doi: 10.1021/jm0580149
Kotali, A., Nasiopoulou, D. A., Tsoleridis, C. A., Harris, P. A., Kontogiorgis, C. A. & Hadjipavlou-Litina, D. J. 2016. Antioxidant Activity of 3-[N-(Acylhydrazono)ethyl]-4-hydroxy-coumarins. Molecules, 21(2), pp. 138. doi: 10.3390/molecules21020138
Krezel, I., Mikiciuk-olasik, E., Zurek, E. & Glowka, M. L. 1999. New Mitoguazone Analogues with Anticancer Activity. Pharmacy and Pharmacology Communications, 5(8), pp. 485-49 0. doi: 10.1211/146080899128735216
Kurteva, V. B., Simeonov, S. P. & Stoilova-Disheva, M. 2011. Symmetrical Acyclic Aryl Aldazines with Antibacterial and Antifungal Activity. Pharmacology & Pharmacy, 2(1), pp. 1-9. doi: 10.4236/pp.2011.21001
Laurin, P., Ferroud, D., Klich, M., Dupuis-Hamelin, C., Mauvais, P., Lassaigne, P., Bonnefoy, A. & Musicki, B. 1999. Synthesis and in vitro evaluation of novel highly potent coumarin inhibitors of gyrase B. Bioorganic & Medicinal Chemistry Letters, 9(14), pp. 2079-2084. doi: 10.1016/s0960-894x(99)00329-7
Lee, C. Y., Nanah, C. N., Held, R. A., Clark, A. R., Huynh, U. G., Maraskine, M. C., Uzarski, R. L., McCracken, J. & Sharma, A. 2015. Effect of electron donating groups on polyphenol-based antioxidant dendrimers. Biochimie, 111, pp. 125-134. doi: 10.1016/j.biochi.2015.02.001
Liang, C., Xia, J., Lei, D., Li, X., Yao, Q., & Gao, J. 2014. Synthesis, in vitro and in vivo antitumor activity of symmetrical bis-Schiff base derivatives of isatin. European Journal of Medicinal Chemistry, 74, pp. 742-750. doi: 10.1016/j.ejmech.2013.04.040
Li, D. Q., Tan, M. X., & Jie, L. 2011. Synthesis, Antioxidant and Antibacterial Activities of Salicylaldehyde Azine. Advanced Materials Research, 396-398, pp. 2366-2369. doi: 10.4028/www.scientific.net/AMR.396-398.2366
López-Rojas, P., Janeczko, M., Kubiński, K., Amesty, Á., Masłyk, M. & Estévez-Braun, A. 2018. Synthesis and Antimicrobial Activity of 4-Substituted 1,2,3-Triazole-Coumarin Derivatives. Molecules, 23(1), pp. 199. doi: 10.3390/molecules23010199
Manolov, I. & Danchev, N. D. 1999. Synthesis, toxicological, and pharmacological assessment of some oximes and aldehyde condensation products of 4-hydroxycoumarin. Archiv der Pharmazie, 332(7), pp. 243-248. doi: 10.1002/(sici)1521-4184(19997)332:7<243::aid-ardp243>3.0.co;2-2
Manolov, I., Maichle-Moessmer, C. & Danchev, N. 2006. Synthesis, structure, toxicological and pharmacological investigations of 4-hydroxycoumarin derivatives. European Journal of Medicinal Chemistry, 41, pp. 882-890. doi: 10.1016/j.ejmech.2006.03.007.
Meanwell, N. A., Roth, H. R., Smith, E. C. R., Wedding, D. L. & Wright, J. J. K. 1991. Diethyl 2,4-dioxoimidazolidine-5-phosphonates: Horner-Wadsworth-Emmons reagents for the mild and efficient preparation of C-5 unsaturated hydantoin derivatives. The Journal of Organic Chemistry, 56(24), pp. 6897-6904. doi: 10.1021/jo00024a036
Medimagh-Saidana, S., Romdhane, A., Daami-Remadi, M., Jabnoun-Khiareddine, H., Touboul, D., Jannet, H. B. & Hamza, M. A. 2015. Synthesis and antimicrobial activity of novel coumarin derivatives from 4-methylumbelliferone. Medicinal Chemistry Research, 24, pp. 3247-3257. doi: 10.1007/s00044-015-1368-y
Nofal, Z. M., El-Zahar, M. I. & Abd El-Karim, S. S. 2000. Novel Coumarin Derivatives with Expected Biological Activity. Molecules, 5(2), pp. 99-113. doi: 10.3390/50200099
Nojiri, S., Daida, H. & Inaba, Y. 2004. Antioxidants and cardiovascular disease: Still a topic of interest. Environmental Health and Preventive Medicine, 9(5), pp. 200-213. doi: 10.1007/BF02898101
Paterna, A., Khonkarn, R., Mulhovo, S., Moreno, A., Girio, P. M., Baubichon-Cortay, H., Falson, P. & Ferreira, M. J. U. 2018. Monoterpene indole alkaloid azine derivatives as MDR reversal agents. Bioorganic & Medicinal Chemistry, 26(2), pp. 421-434. doi: 10.1016/j.bmc.2017.11.052
Qian, Y., Zhang, H-Jia., Lv, P-C. & Zhu, H-L. 2010. Synthesis, molecular modeling and biological evaluation of guanidine derivatives as novel antitubulin agents. Bioorganic & Medicinal Chemistry, 18(23), pp. 8218-8225. doi: 10.1016/j.bmc.2010.10.008
Radulović, N., Stojanović-Radić, Z., Stojanović, N., Stojanović, P., Dekić, V. & Dekić, B. 2015. A small library of 4-(alkylamino)-3-nitrocoumarin derivatives with potent antimicrobial activity against gastrointestinal pathogens, Journal of the Serbian Chemical Society, 15(3), pp. 315-327. doi: 10.2298/JSC140619085R
Ristić, M., Radulović, N., Dekić, B., Dekić, V., Ristić, N. & Stojanović-Radić, Z. 2019. Synthesis and Spectral Characterization of Asymmetric Azines Containing a Coumarin Moiety: The Discovery of New Antimicrobial and Antioxidant Agents. Chemistry & Biodiversity, 16(1), e1800486. doi: 10.1002/cbdv.201800486
Safari. J. & Gandomi-Ravandi, S. 2014. Structure, synthesis and application of azines: a historical perspective. RSC Advances, 4(86), pp. 46224-46249. doi: 10.1039/C4RA04870A
Srivastav, V. K., Tiwari, M. K., Zhang, X. & Yao, X. J. 2018. Synthesis and Antiretroviral Activity of 6-Acetyl-coumarin Derivatives against HIV-1 Infection. Indian Journal of Pharmaceutical Sciences, 80, pp. 108-117. doi: 10.4172/pharmaceutical-sciences.1000335
Subedi, L., Kwon, O. W., Pak, C., Lee, G., Lee, K., Kim, H. & Kim. S. Y. 2017. N,N-disubstituted azines attenuate LPS-mediated neuroinflammation in microglia and neuronal apoptosis via inhibiting MAPK signaling pathways. BMC Neuroscience, 18:82. doi: 10.1186/s12868-017-0399-3
Su, C. X., Mouscadet, J. F., Chiang, C. C., Tsai, H. J. & Hsu, L. Y. 2006. HIV-1 integrase inhibition of biscoumarin analogues. Chemical & Pharmaceutical Bulletin, 54(5), pp. 682-686. doi: 10.1248/cpb.54.682
Tiwari, K., Kumar, S., Kumar, V., Kaur, J., Arora, S. & Mahajan, R. K. 2018. An azine based sensor for selective detection of Cu2+ ions and its copper complex for sensing of phosphate ions in physiological conditions and in living cells. Spectrochimica acta. Part A, Molecular and Biomolecular Spectroscopy, 191, pp. 16-26. doi: 10.1016/j.saa.2017.09.072
Veena, K., Ramaiah, M., Shashikaladevi, K., Avinash, T. S. & Vaidya V. P. 2011. Synthesis and antimicrobial activity of asymmetrical azines derived from naphtho[2,1-b]furan. Journal of Chemical and Pharmaceutical Research, 3(5), pp. 130-135.
Wang, Y. H., Avula, B., Nanayakkara, N. P., Zhao, J. & Khan, I. A. 2013. Cassia cinnamon as a source of coumarin in cinnamon-flavored food and food supplements in the United States. Journal of Agricultural and Food Chemistry, 61(18), pp. 4470-4476. doi: 10.1021/jf4005862
Wei, T., Liang, G., Chen, X., Qi, J., Lin, Q., Zhang, Y. & Yao, H. 2017. A functional applied material on recognition of metal ion zinc based on the double azine compound. Tetrahedron, 73(20), pp. 2938-2942. doi: 10.1016/j.tet.2017.04.001
Zhang, G., Zheng, H., Liu, G., Wang, P., & Xiang, R. 2016. Synthesis and application of a multifunctional fluorescent polymer based on coumarin. BioResources, 11(1), pp. 373-384. doi: 10.15376/biores.11.1.373-384
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