Yeni Benzensülfonamitler ve Benzamitlerin Sentezi, Karbonik Anhidraz ve Kolinerjik Etkilerinin İncelenmesi

Year 2023, , 1814 - 1825, 01.09.2023

Akın Akıncıoğlu

https://doi.org/10.21597/jist.1278301

Abstract

Bu çalışmada, 1-brom-2,4-dimetoksibenzen (8) ve 1-brom-3,5-dimetoksibenzen (10)’dan çıkılarak yeni benzensülfonamit ve benzamit türevleri sentezlendi. Sentezlenen bileşiklerin hCA-I, hCA-II, AChE ve BChE enzimleri üzerine inhibisyon aktiviteleri araştırıldı. Yeni amit türevleri 9 ve 11’in sentezi çıkış bileşikleri 8 ve 10’un CSI ile olan reaksiyonundan gerçekleştirildi. Metoksi substitue benzenlerin aşırı HSO3Cl ile muamelesi, akabinde elde edilen benzen sülfonil klorürlerin amonyakla reaksiyonu sülfonamitler 16 ve 17’yi verdi. Sentezi gerçekleştirilen sülfonamit ve benzamit türevlerinin hCA-I, hCA-II, AChE ve BChE enzimleri üzerine mikromolar seviyede inhibisyon etkisi gösterdikleri belirlenmiş oldu.

Keywords

Benzen sülfonamit, Benzamit, Karbonik Anhidraz, Anti-Alzheimer

Supporting Institution

Ağrı İbrahim Çeçen Üniversitesi Bilimsel Araştırma Projeleri Koordinatörlüğü

Project Number

Proje No: MARŞL.21.01

Thanks

Projeyi maddi olarak destekleyen Ağrı İbrahim Çeçen Üniversitesi BAP Koordinatörlüğüne (Proje No: MARŞL.21.01) ve çalışmanın gerçekleştirildiği Ağrı İbrahim Çeçen Üniversitesi Merkezi Araştırma ve Uygulama Laboratuvarına teşekkür ederim. Biyokimya çalışmaları boyunca bilgi ve deneyiminden faydalandığım Prof. Dr. Hülya AKINCIOĞLU’na teşekkürü bir borç bilirim.

Synthesis of New Benzenesulfonamides and Benzamides, Investigation of Carbonic Anhydrase and Cholinergic Effects

Abstract

In this study, new benzene sulfonamide and benzamide derivatives were synthesized from 1-bromo-2,4-dimethoxybenzene (8) and 1-bromo-3,5-dimethoxybenzene (10). Inhibitory effects of synthesized compounds on hCA-I, hCA-II, AChE and BChE enzymes were investigated. The synthesis of the new amide derivatives 9 and 11 was carried out from the reaction of the starting compounds 8 and 10 with CSI. Treatment of methoxy-substituted benzenes with excess HSO3Cl followed by reaction of the resulting benzene sulfonyl chlorides with ammonia gave sulfonamides 16 and 17. It was determined that the synthesized sulfonamide and benzamide derivatives showed inhibition effect on hCA-I, hCA-II, AChE and BChE enzymes at micromolar level.

Keywords

Benzenesulfonamide, Benzamide, Carbonic Anhydrase, Anti-Alzheimer

Project Number

Proje No: MARŞL.21.01

References

• Abbate, F., Casini, A., Scozzafava, A., Supuran, C.T., (2004). Carbonic anhydrase inhibitors: X-ray crystallographic structure of the adduct of human isozyme II with a topically acting antiglaucoma sulfonamide. Bioorg. Med. Chem. Lett, 14, 2357-2361.
• Akbaba, Y., Akıncıoğlu, A., Göçer, H., Göksu, S., Gülçin, İ., 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.
• Akıncıoğlu, A., Akbaba, Y., Göçer, H., Göksu, S., Gülçin, İ., Supuran, C.T., (2013). Novel sulfamides as potential carbonic anhydrase isoenzymes inhibitors. Bioorg. Med. Chem., 21, 1379–1385.
• Akıncıoğlu, A., Akıncıoğlu, H., Gülçin, İ., Durdagi, S., Supuran, C. T., Göksu, S. (2015). Discovery of potent carbonic anhydrase and acetylcholine esterase inhibitors: novel sulfamoylcarbamates and sulfamides derived from acetophenones. Bioorg. Med. Chem., 23(13), 3592-3602.
• Akurathi, V. Dubois, L. Celen, S. Lieuwes, N.G. Chitneni, S. K. Cleynhens, B.J. Innocenti, A. Supuran, C.T. Verbruggen, A.M., Lambin, P., Bormans, G.M., (2014). Development and biological evaluation of ⁹⁹mTc-sulfonamide derivatives for in vivo visualization of CA IX as surrogate tumor hypoxia markers. Eur. J. Med. Chem., 71, 374–384.
• Alterio V., Fiore D.A., Katia D’Ambrosio, Supuran C.T., Simone G. D., (2012). Multiple Binding Modes of Inhibitors to Carbonic Anhydrases: How to Design Specific Drugs Targeting 15 Different Isoforms?. Chem. Rev., 112, 4421−4468.
• Armstrong, J.M., Myers, D.V., Verpoorte, J.A., Edsall, J.T., (1966). Purification and properties of human erythrocyte carbonic anhydrase. J. Biol. Chem., 214, 5137-5149.
• Arnold, K., Davies, B., Hérault, D., Whiting, A. (2008). Asymmetric direct amide synthesis by kinetic amine resolution: a chiral bifunctional aminoboronic acid catalyzed reaction between a racemic amine and an achiral carboxylic acid. Angew. Chem., Int. Ed., 47(14), 2673-2676.
• Becerra-Figueroa, L., Ojeda-Porras, A., & Gamba-Sanchez, D. (2014). Transamidation of carboxamides catalyzed by Fe (III) and water. J. Org. Chem., 79(10), 4544-4552.
• Beydemir, Ş., Gülçin İ., (2004). Effect of melatonin on carbonic anhydrase from human erythrocyte in vitro and from rat erythrocyte in vivo. J Enzyme Inhib Med Chem, 19, 193-197.
• Boyd, A.E., (1988). Sulfonylurea receptors, ion channels, and fruit flies. Diabetes, 37, 847-850.
• Chandna, N., Kumar, S., Kaushik, P., Kaushik, D., Roy, S.K., Gupta, G.K., Jachak, S. M., Kapoor, J.K., Sharma, P.K., (2013). Synthesis of novel celecoxib analogues by bioisosteric replacement of sulfonamide as potent anti-inflammatory agents and cyclooxygenase inhibitors. Bioorg. Med. Chem., 21, 4581–4590.
• David, G., Wilkinson, P.T., Schwam, E., Parrish, J.P., (2004). Cholinesterase inhibitors used in the treatment of alzheimer’s disease. the relationship between pharmacological effects and clinical efficacy. Drugs Aging, 21, 7, 453-478.
• Ellman, G. L., Courtney, K. D., Andres Jr, V., Featherstone, R. M. (1961). A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical pharmacology, 7(2), 88-95.
• Felicio, L. F., & Nasello, A. G. (1989). Effect of acute bromopride treatment on rat prolactin levels and sexual behavior. Braz J Med Biol Res., 22(8), 1011-1014.
• Ghorab, M.M., Ragab, F.A., Heiba, H.I., El-Hazek, R.M., 2011. Anticancer and radio-sensitizing evaluation of some new thiazolopyrane and thiazolopyranopyrimidine derivatives bearing a sulfonamide moiety. Eur. J. Med. Chem., 46, 5120-5126.
• Ghosh, S. C., Ngiam, J. S., Seayad, A. M., Tuan, D. T., Chai, C. L., Chen, A. (2012). Copper-catalyzed oxidative amidation of aldehydes with amine salts: synthesis of primary, secondary, and tertiary amides. J. Org. Chem., 77(18), 8007-8015.
• Goa, K. L., Barradell, L. B., Plosker, G. L. (1996). Bezafibrate: an update of its pharmacology and use in the management of dyslipidaemia. Drugs, 52, 725-753.
• Gómez-Carpintero, J., Sánchez, J. D., González, J. F., Menéndez, J. C. (2021). Mechanochemical Synthesis of Primary Amides. J. Org. Chem., 86(20), 14232-14237.
• Göçer, H., Akıncıoğlu, A., Öztaşkın, N., Göksu, S., Gülçin, İ. (2013). Synthesis, Antioxidant, and Antiacetylcholinesterase Activities of Sulfonamide Derivatives of Dopamine‐R elated Compounds. Arch. Pharm., 346(11), 783-792.
• Härtter, S., Dingemanse, J., Baier, D., Ziegler, G., Hiemke, C. (1996). The role of cytochrome P450 2D6 in the metabolism of moclobemide. Eur Neuropsychopharmacol., 6(3), 225-230.
• Humphrey, P.P., Feniuk, W., Marriott, A.S., Tanner, R.J., Jackson, M.R., Tuckeri M.L., (1991). Preclinical studies on the anti-migraine drug, sumatriptan. Eur Neurol., 31, 282-290.
• Inoue, K., (2014). Managing adverse effects of glaucoma medications. Clin. Ophthalmol., 8, 903–913. Jenner, P., Maraden, C. D. (1979). The substituted benzamides–a novel class of dopamine antagonists. Life Sci., 25, 479–486.
• Kara, B., (2009). Aldoz redüktaz, α-Amilaz, Monoamin Oksidaz ve Ksantin Oksidaz Enzimlerinin İnhibisyonu, Yüksek Lisans Tezi, İstanbul Üniversitesi, Fen Bilimleri Enstitüsü, İstanbul.
• Kim, D.-K., Lee, J.Y., Lee, N., Ryu, D.H., Kim, J.-S., Lee, S., Choi, J.-Y., Ryu, J.-H., Kim, N.-H., Im, G.-J., Choi, W.-S., Kim, T.-K., (2001). Synthesis and phosphodiesterase inhibitory activity of new sildenafil analogues containing a carboxylic acid group in the 5’-sulfonamide moiety of a phenyl ring. Bioorg. Med. Chem., 9, 3013-3021.
• Kołaczek, A., Fusıarz, I., Iawecka, J., Branowska, D., (2014). Biological activity and synthesis of sulfonamide derivatives: a brief review. CHEMIK, 68, 620–628.
• Liang, Y. J., Lipscom, W. N. (1991). Substrate and inhibitor binding to human carbonic anhydrase II: a theoretical study. Inhibitors in the carbonic anhydrase from biochemistry and physiology and clinical medicine. Weinheim: VCH Publishers, 50-64.
• Lundberg, H., Tinnis, F., Adolfsson, H. (2012). Direct Amide Coupling of Non‐activated Carboxylic Acids and Amines Catalysed by Zirconium (IV) Chloride. Chem. Eur. J., 18(13), 3822-3826.
• Mayer, S. C., Kreft, A. F., Harrison, B., Abou-Gharbia, M., Antane, M., Aschmies, S., Atchison, K., Chlenov, M., Cole, D.C., Comery, T., Diamantidis, G., Ellingboe, J., Fan, K., Galante, R., Gonzales, C., Ho, D.M., Hoke, M. E., Hu, Y., Huryn, D., Jain, U., Jin, M., Kremer, K., Kubrak, D., Lin, M., Lu, P., Magolda, R., Martone, R., Moore, W., Oganesian, A., Pangalos, M. N., Porte, A., Reinhart, P., Resnick, L., Riddell, D.R., Sonnenberg-Reines, J., Stock, J.R., Sun, S., Wagner, E., Wang, T., Woller, K., Xu, Z., Zaleska, M. M., Zeldis, J., Zhang, M., Zhou, H., Jacobsen, J.S., (2008). Discovery of Begacestat, a Notch-1-Sparing γ-Secretase Inhibitor for the Treatment of Alzheimer’s Disease. J. Med. Chem., 51, 7348–7351.
• Mitsudome, T., Mikami, Y., Mori, H., Arita, S., Mizugaki, T., Jitsukawa, K., Kaneda, K. (2009). Hydration of Nitriles to Amides with Supported Silver Nanoparticles. Synfacts, 2009(10), 1167-1167.
• Gök, N., Akıncıoğlu, A., Erümit Binici, E., Akıncıoğlu, H., Kılınç, N., Göksu, S. (2021). Synthesis of novel sulfonamides with anti‐Alzheimer and antioxidant capacities. Arch. Pharm., 354(7), 2000496.
• Pandya, R., Takashi, M., Tedeschi, L., Barrett, A.G.M., (2003). Facile One-Pot Synthesis of Aromatic and Heteroaromatic Sulfonamides. J. Org. Chem., 68, 8274-8276.
• Rahavi Ezabadi, I., Camoutsis, C., Zoumpoulakis, P., Geronikaki, A., Soković, M., Glamočilija, J., Čirič, A., (2008). Sulfonamide-1,2,4-triazole derivatives as antifungal and antibacterial agents: Synthesis, biological evaluation, lipophilicity, and conformational studies. Bioorg. Med. Chem., 16, 1150-1161.
• Rao, S. N., Mohan, D. C., Adimurthy, S. (2014). Chitosan: an efficient recyclable catalyst for transamidation of carboxamides with amines under neat conditions. Green Chemistry, 16(9), 4122-4126.
• Roush, W.R., Gwaltney, S.L., Cheng, J., Scheidt, K. A., McKerrow, J.H., Hansell, E., (1998). Vinyl Sulfonate Esters and Vinyl Sulfonamides: Potent, Irreversible Inhibitors of Cysteine Proteases. J. Am. Chem. Soc., 120, 10994-10995.
• Temperini, C., Cecchi, A., Scozzafava, A., Supuran, C. T. (2008). Carbonic anhydrase inhibitors. Sulfonamide diuretics revisited—old leads for new applications?. Org. Biomol. Chem., 6(14), 2499-2506.
• Thiry, A., Dogné, J.M., Supuran, C.T., Masereel, B., (2008). Anticonvulsant sulfonamides/sulfamates/sulfamides with carbonic anhydrase inhibitory activity: drug design and mechanism of action. Curr Pharm Des., 14, 661-671.
• Uenoyama, Y., Fukuyama, T., Nobuta, O., Matsubara, H., Ryu, I. (2005). Alkyne Carbonylation by Radicals: Tin‐Radical‐Catalyzed Synthesis of α‐Methylene Amides from 1‐Alkynes, Carbon Monoxide, and Amines. Angew. Chem., Int. Ed., 117(7), 1099-1102.
• Verpoorte, J.A., Mehta, S., Edsall, J.T., (1967). Esterase activities of human carbonic anhydrases. B and C. J. Biol. Chem., 242, 4221-4229.