Potansiyel karbonik anhidraz I ve II inhibitör keşfi: D-Penisilamin türevleri

Year 2024, , 274 - 282, 15.03.2024

Işıl Nihan Korkmaz

https://doi.org/10.17714/gumusfenbil.1359988

Abstract

Protein yapısına katılmayan bir aminoasit türevi olan penisilamin; bir karboksilik asit, bir tiyol ve aminden oluşan üç işlevli bir organik moleküldür. Başta Wilson hastalığı olmak üzere birçok hastalığın tedavisinde kullanılan D-Penisilamin (PEN-1), N-Asetil-D-Penisilamin (PEN-2) ve D-Penisilamin disülfit (PEN-3) in vitro koşullarda karbonik anhidraz I ve II (hCA I, hCA II) izoezimleri üzerindeki inhibisyon etkileri araştırıldı. İnsan eritrosit hücrelerinden hCA I, hCA II enzimleri izole edildi. Saflaştırılan her iki enzimin D-Penisilamin ve türevleri tarafından etkili bir şekilde inhibe edildiği belirlendi. PEN-1, PEN-2 ve PEN-3 moleküllerinin IC50 değerleri hCA I için sırasıyla 387.21; 407.49 ve 106.75 µM, hCA II için sırasıyla 563.72; 364.87 ve 136.91 µM olarak hesaplandı. Bütün moleküller için inhibisyon tipi her iki enzimde de yarışmalı inhibisyon olarak belirlendi.

Keywords

Afinite kromatografisi, İnhibisyon, Karbonik anhidraz, Penisilamin

Discovery of potential carbonic anhydrase I and II inhibitors: D-Penicillamine derivatives

Abstract

Penicillamine, an amino acid derivative that does not participate in the protein structure, is a trifunctional organic molecule composed of a carboxylic acid, a thiol, and an amine. D-Penicillamine (PEN-1), N-Acetyl-D-Penicillamine (PEN-2) and D Penicillamine disulfide (PEN-3), which are used in the treatment of many diseases, especially Wilson's disease, are produced by carbonic anhydrase I and II (hCA I) in vitro. Inhibition effects on hCA II) isoenzymes were investigated. hCA I, hCA II enzymes were isolated from human erythrocyte cells. It was determined that PEN-1, PEN-2, and PEN-3 effectively inhibited both purified enzymes. The IC50 values of PEN-1, PEN-2, and PEN-3 molecules were calculated to be 387.21, 407.49, and 106.75 µM for hCA I, 563.72 364.87, and 136.91 µM for hCA II, respectively. The inhibition type for all molecules was determined as competitive inhibition in both enzymes.

Keywords

Affinity chromatography, Inhibition, Carbonic anhydrase, Penicillamine

References

• Adem, S., Akkemik, E., Aksit, H., Guller, P., Tüfekci, A. R., Demirtas, İ., & Ciftci, M. (2019). Activation and inhibition effects of some natural products on human cytosolic CAI and CAII. Medicinal Chemistry Research, 28, 711-722.
• 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. Journal of Enzyme Inhibition and Medicinal Chemistry, 29(1), 35-42.
• Akbaba, Y., Balaydın, H. T., Menzek, A., Göksu, S., Şahin, E., & Ekinci, D. (2013). Synthesis and biological evaluation of novel bromophenol derivatives as carbonic anhydrase inhibitors. Archiv der Pharmazie, 346(6), 447-454.
• Akbaba, Y., Bastem, E., Topal, F., Gülçin, İ., Maraş, A., & Göksu, S. (2014). Synthesis and carbonic anhydrase inhibitory effects of novel sulfamides derived from 1‐aminoindanes and anilines. Archiv der Pharmazie, 347(12), 950-957.
• Akbaba, Y., & Kalin, R. (2022). Desıgn, synthesıs, bıologıcal evaluatıon, and ın sılıco study of novel urea derıvatıves as ınhıbıtors of carbonıc anhydrase and acetylcholıne esterase. Studia Universitatis Babes-Bolyai, Chemia, 67(2).
• Alım, Z., Köksal, Z., & Karaman, M. (2020). Evaluation of some thiophene-based sulfonamides as potent inhibitors of carbonic anhydrase I and II isoenzymes isolated from human erythrocytes by kinetic and molecular modelling studies. Pharmacological Reports, 72, 1738-1748.
• Argan, O., Çıkrıkçı, K., & Gencer, N. (2022). Sıvı kardiyak ilaçların karbonik anhidraz I ve II izoenzimleri üzerindeki etkileri. Balıkesir Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 24(2), 545–554.
• Bhushan, R., & Kumar, R. (2010). Enantioresolution of dl‐penicillamine. Biomedical Chromatography, 24(1), 66-82.
• Bibi, S., Javed, T., Alam, F., Ali, A., Ali, S., Ullah, M., Asad, H. Bin, Hassham, M., Hasan, F., & Muhammad, S. (2019). Therapeutic potential of carbonic anhydrase inhibitors. Pakistan Journal of Pharmaceutical Sciences, 32(2).
• Budimir, A. (2011). Metal ions, Alzheimer's disease and chelation therapy. Acta Pharmaceutica, 61(1), 1-14.
• Chipiso, K., Duca, T., & Simoyia, R. H. (2019). Kinetics and mechanism of oxidation of N-acetyl-d-penicillamine in acidified iodate and aqueous iodine. South African Journal of Chemistry, 72, 1-9.
• Chong, C. R., & Auld, D. S. (2000). Inhibition of carboxypeptidase A by D-penicillamine: mechanism and implications for drug design. Biochemistry, 39(25), 7580-7588.
• Durmaz, L. (2022). İnterferon Beta-1a ilacının enzim inhibisyon etkilerinin incelenmesi. Journal of the Institute of Science and Technology, 12(4), 2331-2339.
• Friedman, M. (2004). Applications of the ninhydrin reaction for analysis of amino acids, peptides, and proteins to agricultural and biomedical sciences. Journal of Agricultural and Food Chemistry, 52(3), 385-406.
• Genç, H., Kalin, R., Köksal, Z., Sadeghian, N., Kocyigit, U. M., Zengin, M., ... & Özdemir, H. (2016). Discovery of potent carbonic anhydrase and acetylcholinesterase inhibitors: 2-aminoindan β-lactam derivatives. International Journal of Molecular Sciences, 17(10), 1736.
• Gulcin, I., & Beydemir, S. (2013). Phenolic compounds as antioxidants: carbonic anhydrase isoenzymes inhibitors. Mini Reviews in Medicinal Chemistry, 13(3), 408–430.
• Güller, P., Atmaca, U., Güller, U., Çalışır, U., & Dursun, F. (2021). Antibacterial properties and carbonic anhydrase inhibition profiles of azido sulfonyl carbamate derivatives. Future Medicinal Chemistry, 13(15), 1285-1299.
• Güller, P., Dağalan, Z., Güller, U., Çalışır, U., & Nişancı, B. (2021). Enzymes inhibition profiles and antibacterial activities of benzylidenemalononitrile derivatives. Journal of Molecular Structure, 1239, 130498.
• Jonsson, B. H., & Liljas, A. (2020). Perspectives on the classical enzyme carbonic anhydrase and the search for inhibitors. Biophysical Journal, 119(7), 1275-1280.
• Karioti, A., Carta, F., & Supuran, C. T. (2016). Phenols and polyphenols as carbonic anhydrase inhibitors. Molecules, 21(12), 1649.
• Kark, R. A. P., Poskanzer, D. C., Bullock, J. D., & Boylen, G. (1971). Mercury poisoning and its treatment with N-acetyl-D, L-penicillamine. New England Journal of Medicine, 285(1), 10–16.
• Kazancı, A., Gök, Y., Kaya, R., Aktaş, A., Taslimi, P., & Gülçin, İ. (2021). Synthesis, characterization and bioactivities of dative donor ligand N-heterocyclic carbene (NHC) precursors and their Ag (I) NHC coordination compounds. Polyhedron, 193, 114866.
• Kean, W. F., Howard-Lock, H. E., & Lock, C. J. L. (1991). Chirality in antirheumatic drugs. The Lancet, 338(8782-8783), 1565-1568. Kocak, R., Akın, E. T., Kalın, P., Talaz, O., Saracoglu, N., Dastan, A., Gülçin, İ., & Durdagi, S. (2016). Synthesis of some novel norbornene‐fused pyridazines as potent inhibitors of carbonic anhydrase and acetylcholinesterase. Journal of Heterocyclic Chemistry, 53(6), 2049–2056.
• Korkmaz, I. N. (2023). 2‐Amino thiazole derivatives as inhibitors of some metabolic enzymes: An in vitro and in silico study. Biotechnology and Applied Biochemistry, 70(2), 659-669.
• Köksal, Z., Alım, Z., Bayrak, S., Gülçin, İ., & Özdemir, H. (2019). Investigation of the effects of some sulfonamides on acetylcholinesterase and carbonic anhydrase enzymes. Journal of Biochemical and Molecular Toxicology, 33(5), e22300.
• Kucukoglu, K., Oral, F., Aydin, T., Yamali, C., Algul, O., Sakagami, H., Gulcin, I., Supuran, C. T., & Gul, H. I. (2016). Synthesis, cytotoxicity and carbonic anhydrase inhibitory activities of new pyrazolines. Journal of Enzyme Inhibition and Medicinal Chemistry, 31(sup4), 20–24.
• Kumar, S., Rulhania, S., Jaswal, S., & Monga, V. (2020). Recent advances in the medicinal chemistry of carbonic anhydrase inhibitors. European Journal of Medicinal Chemistry, 112923.
• Laemmli, D. K. (1970). Cleavage of structural proteins during in assembly of the head. Nature, 227, 680–683.
• Munro, R., & Capell, H. A. (1997). Penicillamine. British Journal of Rheumatology, 36(1), 104–109.
• Özyürek, İ., Kalın, R., & Özdemir, H. (2020). D-Penisilamin, D-Penisilamin disülfit ve N-Asetil-D-penisilamin’in Laktoperoksidaz Enzim Aktivitesi Üzerine İnhibisyon Etkileri. Journal of the Institute of Science and Technology, 10(2), 1146–1153.
• Phelps, D. L., Lakatos, L., & Watts, J. L. (2000). D-Penicillamine for preventing retinopathy of prematurity in preterm infants. The Cochrane Database of Systematic Reviews, 2, CD001073–CD001073.
• Supuran, C. T. (2020). An update on drug interaction considerations in the therapeutic use of carbonic anhydrase inhibitors. Expert Opinion on Drug Metabolism & Toxicology, 16(4), 297–307.
• Verpoorte, J. A., Mehta, S., & Edsall, J. T. (1967). Esterase activities of human carbonic anhydrases B and C. Journal of Biological Chemistry, 242(18), 4221–4229.