Design, Synthesis and Biological Activities of Chalcones with Piperonal Moiety

Year 2020, , 620 - 630, 31.08.2020

Mehtap Tuğrak , Halise İnci Gül , Barış Anıl , Hülya Akıncıoğlu

https://doi.org/10.18185/erzifbed.698849

Abstract

Heterosiklik bileşikler, farmakolojik olarak aktif bileşikler arasında özel bir öneme sahiptir. Bu çalışmada, bazı piperonal bazlı şalkonlar (PC1-PC10), 3,4-metilendioksibenzaldehid ve birkaç asetofenon arasında Claisen-Schmidt Kondenzasyonu ile sentezlendi. Bileşiklerin inhibitör etkileri, insan karbonik anhidraz I, II enzimlerine (hCA I ve hCA II) ve asetilkolinesteraz (AChE) enzimine karşı araştırıldı. Şalkon türevlerinin, hCA I için 5.11-109.70 μM, hCA II için 17.05-162.59 μM ve AChE için 18.52-98.69 μM aralığında IC50 değerlerine sahip olduğu görüldü. Tüm bileşikler referans bileşiklerden daha düşük inhibisyon potansiyeli gösterdi. Fakat PC3 (metoksi) hCA I ve hCA II karşı, PC5 (flor) AChE'ye karşı söz konusu yeni daha güçlü bileşikler geliştirmek için serinin aday bileşikleri olarak belirlendi.

Keywords

Alzheimer disease, chalcone, carbonic anhydrase, piperonal, acetylcholinesterase

Piperonal Artığı Taşıyan Şalkonların Dizaynı, Sentezi ve Biyolojik Aktiviteleri

Abstract

Heterosiklik bileşikler, farmakolojik olarak aktif bileşikler arasında özel bir öneme sahiptir. Bu çalışmada, bazı piperonal bazlı şalkonlar (PC1-PC10), 3,4-metilendioksibenzaldehid ve birkaç asetofenon arasında Claisen-Schmidt Kondenzasyonu ile sentezlendi. Şalkonların inhibisyon potansiyelleri insan karbonik anhidraz I, II enzimlerine (hCA I ve hCA II) ve asetilkolinesteraz (AChE) enzimine karşı araştırıldı. Şalkon türevlerinin, hCA I için 5.11-109.70 μM, hCA II için 17.05-162.59 μM ve AChE için 18.52-98.69 μM aralığında IC50 değerlerine sahip olduğu görüldü. Tüm bileşikler referans bileşiklerden daha düşük inhibisyon potansiyeli gösterdi. PC3 (metoksi türevi) bileşiği hem hCA I hemde hCA II’ye karşı en etkili bileşik olurken, PC5 (flor türevi) AChE'ye karşı seri içinde en güçlü inhibitör etki göstermiştir. Sonuçlar, şalkon türevleri PC3 ve PC5'in hCA I, hCA II ve AChE izoenzimlerine karşı daha güçlü enzim inhibitörleri tasarlamada uygun adaylar olarak kabul edilebileceğini doğrulamıştır.

Keywords

Alzheimer Hastalığı, karbonik anhidraz,, şalkon

References

• References Akbaba, Y., Akincioglu, A., Gocer, H., Goksu, S., Gulcin, I., & Supuran, C. T. 2014. ''Carbonic anhydrase inhibitory properties of novel sulfonamide derivatives of aminoindanes and aminotetralins'', J Enzyme Inhib Med Chem, 29(1), 35-42.
• Attanayake, A.P., Jayatilaka, K. A. P. W. 2018. ''Acetylcholinesterase Inhibitory Activity And Antioxidant Activity of Selected Medicinal Plant Extracts Used Against Cognitive Dysfunction And Memory Loss In Sri Lankan Traditional Medicine'', Asian Journal of Pharmaceutical Research and Development, 6(5), 16-25.
• Asrar A.A., Hussain, M. S. M. M. 2018. ''Synthesis And Evaluation Of Piperonal Chalcone And Its Derivatives As Anti-Diabetic Agents'', European Journal of Biomedical and Pharmaceutical sciences, 5(2), 514-518.
• Jithan, A.V., Keerthana, E., Venkanna, P., Venumadhav, K., Reddy, K. S. 2009. ''Synthesis of novel piperonal derivatives and evaluation of their anticonvulsant activity using a nanoparticular formulation'', International journal of pharmaceutical sciences and nanotechnology, 2(1), 435-442.
• Bai, P., Wang, K. R., Zhang, P. F., Shi, J., Cheng, X. F., Zhang, Q., Sang, Z. P. 2019. ''Development of chalcone-O-alkylamine derivatives as multifunctional agents against Alzheimer's disease'', European Journal of Medicinal Chemistry, 183, 111737 Bradford, M. M. 1976. ''A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding'', Anal Biochem, 72, 248-254.
• Burmaoglu, S., Yilmaz, A. O., Taslimi, P., Algul, O., Kilic, D., Gulcin, I. 2018. ''Synthesis and biological evaluation of phloroglucinol derivatives possessing alpha-glycosidase, acetylcholinesterase, butyrylcholinesterase, carbonic anhydrase inhibitory activity''. Arch Pharm (Weinheim), 351(2). doi: 10.1002/ardp.201700314
• Chiaradia, L. D., Mascarello, A., Purificacao, M., Vernal, J., Cordeiro, M. N. S., Zenteno, M. E., Terenzi, H. 2008. ''Synthetic chalcones as efficient inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatase PtpA'', Bioorganic & Medicinal Chemistry Letters, 18(23), 6227-6230.
• Diaz-Rubio, L., Hernandez-Martinez, R., Estolano-Cobian, A., Chavez-Velasco, D., Salazar-Aranda, R., de Torres, N. W., Cordova-Guerrero, I. 2019. ''Synthesis, Biological Evaluation and Docking Studies of Chalcone and Flavone Analogs as Antioxidants and Acetylcholinesterase Inhibitors'', Applied Sciences-Basel, 9(3). doi: ARTN 410 10.3390/app9030410 Ellman, G. L., Courtney, K. D., Andres, V., Jr., Feather-Stone, R. M. 1961. ''A new and rapid colorimetric determination of acetylcholinesterase activity''. Biochem Pharmacol, 7, 88-95. Gul, H. I., Tugrak, M., Gul, M., Mazlumoglu, S., Sakagami, H., Gulcin, I., & Supuran, C. T. 2019. ''New phenolic Mannich bases with piperazines and their bioactivities'', Bioorg Chem, 90, 103057.
• Lineweaver, H., Burk, D. 1934. ''The determination of enzyme dissociation constants'', J. Am. Chem. Soc, 56, 658-666. Hasan, A. H., Amran, S. I., Hussain, F. H. S., Jaff, B. A., Jamalis, J. 2019. ''Molecular Docking and Recent Advances in the Design and Development of Cholinesterase Inhibitor Scaffolds:CoumarinHybrids'', Chemistryselect, 4(48), 14140-14156.
• Nunez-Borque, E., Gonzalez-Naranjo, P., Bartolome, F., Alquezar, C., Reinares-Sebastian, A., Perez, C., Martin-Requero, A. 2020. ''Targeting Cannabinoid Receptor Activation and BACE-1 Activity Counteracts TgAPP Mice Memory Impairment and Alzheimer's Disease Lymphoblast Alterations'', Molecular Neurobiology. doi: 10.1007/s12035-019-01813-4
• Ozgun, D. O., Yamali, C., Gul, H. I., Taslimi, P., Gulcin, I., Yanik, T., Supuran, C. T. 2016. ''Inhibitory effects of isatin Mannich bases on carbonic anhydrases, acetylcholinesterase, and butyrylcholinesterase'', Journal of Enzyme Inhibition and Medicinal Chemistry, 31(6), 1498-1501. Pal, R. 2013. ''Ammonium chloride catalyzed microwave-assisted Claisen-Schmidt reaction between ketones and aldehydes under solvent-free conditions'', IOSR Journal of Applied Chemistry, 3(4), 74-80.
• Pathak, V. N., Oza, C. K., Gupta, R., Tiwari, R., Chaudhary, S. 2003. ''Synthesis and spectral studies of some new bis(1,3-diketonato)palladium(II) complexes'', Synthesis and Reactivity in Inorganic and Metal-Organic Chemistry, 33(4), 607-624.
• Reddy, M. V. B., Hung, H. Y., Kuo, P. C., Huang, G. J., Chan, Y. Y., Huang, S. C., Wu, T. S. 2017. ''Synthesis and biological evaluation of chalcone, dihydrochalcone, and 1,3-diarylpropane analogs as anti-inflammatory agents'', Bioorganic & Medicinal Chemistry Letters, 27(7), 1547-1550.
• Shukla, R., Singh, T. R. 2020. ''Virtual screening, pharmacokinetics, molecular dynamics and binding free energy analysis for small natural molecules against cyclin-dependent kinase 5 for Alzheimer's disease'', Journal of Biomolecular Structure & Dynamics, 38(1), 248-262.
• Supuran, C. T. 2008. ''Carbonic anhydrases: novel therapeutic applications for inhibitorsand activators'', Nat. Rev. Drug. Discov, 7, 168-181.
• Tian, C. Q., Qiang, X. M., Song, Q., Cao, Z. C., Ye, C. Y., He, Y. X., Zhang, L. 2020. ''Flurbiprofen-chalcone hybrid Mannich base derivatives as balanced multifunctional agents against Alzheimer's disease: Design, synthesis and biological evaluation'', Bioorganic Chemistry, 94. doi: ARTN 10347710.1016/j.bioorg.2019.103477 Timur, I., Kocyigit, U. M., Dastan, T., Sandal, S., Ceribasi, A. O., Taslimi, P., . . . Ciftci, M. 2019. ''In vitro cytotoxic and in vivo antitumoral activities of some aminomethyl derivatives of 2,4-dihydro-3H-1,2,4-triazole-3-thiones-Evaluation of their acetylcholinesterase and carbonic anhydrase enzymes inhibition profiles'', Journal of Biochemical and Molecular Toxicology, 33(1). doi: ARTN e2223910.1002/jbt.22239 Tugrak, M., Gul, H. I., Bandow, K., Sakagami, H., Gulcin, I., Ozkay, Y., & Supuran, C. T. 2019. ''Synthesis and biological evaluation of some new mono Mannich bases with piperazines as possible anticancer agents and carbonic anhydrase inhibitors''. Bioorg Chem, 90, 103095. doi: 10.1016/j.bioorg.2019.103095
• Tugrak, M., Inci Gul, H., Sakagami, H., Gulcin, I., & Supuran, C. T. 2018. ''New azafluorenones with cytotoxic and carbonic anhydrase inhibitory properties: 2-Aryl-4-(4-hydroxyphenyl)-5H-indeno[1,2-b]pyridin-5-ones''. Bioorg Chem, 81, 433-439.
• Verpoorte, J. A., Mehta, S., Edsall, J. T. 1967. ''Esterase activities of human carbonic anhydrases B and C'', J Biol Chem, 242(18), 4221-4229.
• Yamali, C., Gul, H. I., Ece, A., Taslimi, P., & Gulcin, I. 2018. ''Synthesis, molecular modeling, and biological evaluation of 4-[5-aryl-3-(thiophen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl] benzenesulfonamides toward acetylcholinesterase, carbonic anhydrase I and II enzymes'', Chemical Biology & Drug Design, 91(4), 854-866.
• Yamali, C., Gul, H. I., Ozgun, D. O., Sakagam, H., Umemura, N., Kazaz, C., & Gul, M. 2017. ''Synthesis and Cytotoxic Activities of Difluoro-Dimethoxy Chalcones''. Anticancer Agents Med Chem, 17(10), 1426-1433.
• Yamali, C., Gul, H. I., Sakagami, H., & Supuran, C. T. 2016. ''Synthesis and bioactivities of halogen bearing phenolic chalcones and their corresponding bis Mannich bases''. J Enzyme Inhib Med Chem, 31(sup4), 125-131.