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Evaluation of Some Sulfonamide Derivatives as a Potential Inhibitors of The Carbonic Anhydrase IX/XII by ADME and Molecular Docking Method

Yıl 2022, Cilt: 12 Sayı: 1, 88 - 105, 30.06.2022
https://doi.org/10.37094/adyujsci.1091227

Öz

Molecular docking is a simulation technique that calculates the binding score of the molecules of interest to protein structures and visualizes the bond structure. It is a widely used technique for foresight because it helps to determine bond relationships between molecular structures before laboratory applications in the development of new drugs. ADME studies also provide clues for the determination of the molecules analyzed by the molecular docking method to be drug candidates. In this study, inhibition of CA IX and CA XII enzymes by sulfonamide derivatives synthesized in our previous study was investigated using molecular docking method. The CA enzyme family has an important role in the survival and spread of cancer cells. Therefore, we aimed to find new drug candidates that inhibit these enzymes. We found that the sulfonamide derivative named 6 binds to the active sites of both CA IX and CA XII enzymes with -7.44 kcal/mol and -6.39 kcal/mol energy, respectively, closest to the binding of the reference molecule acetazolamide. In addition, the compatibility of all compounds used in the study with drug-like properties was investigated using the ADME method. In conclusion, it can be said that the sulfonamide derivatives named 1-9 generally have the characteristic features of a drug (physicochemical and structural properties) and oral bioavailability.

Kaynakça

  • [1] Andreucci, E., Ruzzolini, J., Peppicelli, S., Bianchini, F., Laurenzana, A., Carta, F., Supuran, C.T., Caalorini, L., The carbonic anhydrase IX inhibitor SLC-0111 sensitises cancer cells to conventional chemotherapy, Journal of Enzyme Inhibition and Medicinal Chemistry, 34(1), 117-123, 2019.
  • [2] Supuran, C.T., Scozzafava, A., Carbonic anhydrase inhibitors and their therapeutic potential, Expert Opinion on Therapeutic Patents, 10(5), 575-600, 2000.
  • [3] Supuran, C.T., Structure and function of carbonic anhydrases, Biochemical Journal, 473, 2023–2032, 2016.
  • [4] Alterio, V., Hilvo, M., Di Fiore, A., Supuran, C.T., Pan, P., Parkkila, S., Scaloni, A., et al., Crystal structure of the catalytic domain of the tumor-associated human carbonic anhydrase IX, PNAS, 106(38), 16233-16238, 2009.
  • [5] Chegwidden, W.R., Carter, N.D., Edwards Y.H., The carbonic anhydrases, Birkhauser, Boston, 2000.
  • [6] Sly, W.S., Hu P.Y., Human carbonic anhydrases and carbonic anhydrase deficiencies, Annual Review of Biochemistry, 64, 375-401, 1995.
  • [7] Supuran, C.T., Scozzafava, A., Carbonic Anhydrase Inhibitors, Current Medicinal Chemistry, 363(1), 61-97, 2001.
  • [8] Supuran, C.T., Scozzafava, A., Carbonic anhydrases as targets for medicinal chemistry, Bioorganic & Medicinal Chemistry, 15, 4336–4350, 2007.
  • [9] Stadie, W.C., O’Brien, H., The catalytic of the hydration of carbon dioxide and dehydration of carbonic acid by an enzyme isolated from red blood cells, Journal of Biological Chemistry, 103, 521–529, 1933.
  • [10] Wassel, M.M.S., Ragab, A. et al., Novel adamantine-pyrazole and hydrazine hybridized: design, synthesis, cytotoxic evaluation, SAR study and molecular docking simulation as carbonic anhydrase inhibitors, Journal of Molecular Structure, 1223, 128966, 2021.
  • [11] Svastová, E., Hulíková, A., Rafajová, M., Zat’Ovicˇová, M., Gibadulinová, A., Casini, A., Cecchi, A., Scozzafava, A., Supuran, C.T., Pastorek, J., et al., Hypoxia activates the capacity of tumor-associated carbonic anhydrase IX to acidify extracellular pH, FEBS Letters, 577, 439– 445, 2004. [12] Koyuncu, I., Temiz, E., Durgun, M., Kocyigit, A., Yuksekdag, O., Supuran, C.T., Intracellular pH-mediated induction of apoptosis in HeLa cells by a sulfonamide carbonic anhydrase inhibitor, International Journal of Biological Macromolecules, 2022. [13] Temiz, E., Koyuncu, I., Durgun, M., Caglayan, M., Gonel, A., Güler, E. M., Kocyigit, Supuran, C.T., Inhibition of carbonic anhydrase IX promotes apoptosis through intracellular PH level alterations in cervical cancer cells. International Journal of Molecular Sciences, 22(11), 6098, 2021.
  • [14] Durgun, M., Turkmen, H., Zengin, G., Zengin, H., Koyunsever, M., Koyuncu, I., Synthesis, characterization, in vitro cytotoxicity and antimicrobial investigation and evaluation of physicochemical properties of novel 4-(2-methylacetamide) benzenesulfonamide derivatives, Bioorganic Chemistry, 70, 163-172, 2017.
  • [15] Chohan, Z.H., Hassan, M., Khan, K.M., Supuran, C.T., In-vitro antibacterial, antifungal and cytotoxic properties of sulfonamide derived Schiff’s bases and their metal complexes, Journal of Enzyme Inhibition and Medicinal Chemistry, 20(2), 183-188, 2004.
  • [16] Connor, E.E., Sulfonamide antibiotics, Primary Care Update for OB/GYNS, 5(1), 32- 35, 1998.
  • [17] Turkmen, H., Zengin, G., Buyukkircali, B., Synthesis of sulfonamide derivatives and investigation of in vitro inhibitory activities and antimicrobial and physical properties, Bioorganic Chemistry, 39(3), 114-119, 2011.
  • [18] Durgun, M., Zengin, G., Zengin, H., Koyuncu, I., Turkoglu, S., Sonmez, H., Kuru, A., Synthesis, characterization, cytotoxicity evaluation and physicochemical properties of some novel N4-substituted aminobenzenesulfonamides, Indian Journal of Chemistry, 60B, 888-900, 2021.
  • [19] Morris, G.M. et al., Auto dock 4 and auto dock tools 4: automated docking with selective receptor flexibility, Journal of Computational Chemistry, 30, 2785–91, 2009.
  • [20] Hanwell, M.D., Curtis, D.E., Lonie, D.C., Vandermeersch, T., Zurek, E., Hutchison, G.R., Avogadro: an advanced semantic chemical editor, visualization, and analysis platform, Journal of Cheminformatics, 4, 17, 2012.
  • [21] Daina, A., Michielin, O., Zoete, V., SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules, Scientific Reports, 7, 42717, 2017.
  • [22] Mishra, S., Dahima, R., In-vitro ADME studies of TUG-891, a GPR-120 inhibitor using Swiss ADME predictor, Journal of Drug Delivery and Therapeutics, 9(2-s), 266-369, 2019.
  • [23] Farzam, K., Abdullah, M., Acetazolamide. StatPearls Publishing, Treasure Island (FL), 2022.
  • [24] Opavsky, R., Pastorekova, S., Zelnık, V., Gibadulinova, A., Stanbridge, E.J., Zavada, J., Kettmann, R., Pastorek, J., Human MN/CA9 gene, a novel member of the carbonic anhydrase family: structure and exon to protein domain relationships, Genomics, 33, 480–487, 1996.
  • [25] Hilvo, M., Baranauskiene, L., Salzano, A.M., Scaloni, A., Matulis, D., Innocenti, A., Scozzafava, A., Monti, S.M., Di Fiore, A., De Simone, G., Lindfors, M., Janis, J., Valjakka, J., Pastorekova, S., Pastorek, J., Kulomaa, M.S., Nordlund, H.R., Supuran, C.T., Parkkila, S., Biochemical characterization of CA IX, one of the most active carbonic anhydrase isozymes. Journal of Biological Chemistry, 283, 27799–27809, 2008.
  • [26] Boyluğ, Z.E., Yoğunluk Fonksiyonel Teori Temelli Kantitatif Yapi-Etki Analizleri (QSAR): Kumarin Moleküllerinin Karbonik Anhidraz Enzimine Karşi İnhibisyon Etkisinin Modellenmesi. MSc Thesis, Aksaray University, Aksaray, Turkey, 2016.
  • [27] Supuran, C.T., Scozzafava, A., Casini, A., Carbonic anhydrase inhibitors, Medicinal Research Reviews, 23(2), 146–189, 2003.
  • [28] Stams, T., Christianson, D.W., In the carbonic anhydrases. new horizons; Chegwidden, W.R., Carter, N.D., Edwards, Y.H., Eds. Birkhaüser Verlag: Basel, Switzerland, 159p., 2000.
  • [29] Lindahl, M., Vidgren, J., Eriksson, E., Habash, J., Harrop, S., Helliwell, J., Liljas, A., Lindeskog, M., Walker, N., In Carbonic Anhydrase: From Biochemistry and Genetics to Physiology and Clinical Medicine, Botre, F., Gros, G., Storey, B.T., Eds. VCH: Weinheim, Germany, 111p., 1991.
  • [30] Özensoy, Ö., Kanser ile ilişkili Karbon Anhidraz IX ve XII izoenzimlerinin (CA-IX, CA-XII) ekspresyonu, saflaştırılması ve bazı bileşiklere karşı inhibisyon etkilerinin araştırılması, PhD Thesis, Balıkesir University, Balıkesir, Turkey, 2006.
  • [31] Eckert, A.W., Lautner, M.H., Schutze, A., Bolte, K., Bache, M., Kappler, M., Schubert, J., Taubert, H., Bilkenroth, U., Co-expression of Hif1alpha and CA IX is associated with poor prognosis in oral squamous cell carcinoma patients, Journal of Oral Pathology and Medicine, 39, 313–317, 2010.

Karbonik Anhidraz IX/XII'nin Potansiyel İnhibitörleri Olarak Bazı Sülfonamit Türevlerinin ADME ve Moleküler Yerleştirme Metodu ile Değerlendirilmesi

Yıl 2022, Cilt: 12 Sayı: 1, 88 - 105, 30.06.2022
https://doi.org/10.37094/adyujsci.1091227

Öz

Moleküler yerleştirme, ilgili moleküllerin protein yapılarına bağlanma enerjilerini hesaplayan ve bağ yapısını görselleştiren bir simülasyon tekniğidir. Çeşitli hastalıklara ilişkin yeni ilaçların keşfi ve geliştirilmesinde, laboratuvar uygulamalarından önce moleküler yapılar arasındaki bağlanmaları belirlemeye yardımcı olması sebebiyle, yaygın olarak kullanılan bir tekniktir. ADME çalışmaları da moleküler yerleştirme yöntemiyle analiz edilen moleküllerin ilaç adayı olma özelliklerinin belirlenmesinde ipuçları sağlamaktadır. Bu çalışmada, daha önceki çalışmamızda sentezlenen sülfonamit türevleri tarafından CA IX ve CA XII enzimlerinin inhibisyonu, moleküler yerleştirme yöntemi kullanılarak araştırılmıştır. Karbonik anhidraz (CA) enzim ailesi, kanser hücrelerinin hayatta kalmasında ve yayılmasında önemli bir role sahiptir. Bu nedenle bu enzimleri inhibe eden yeni ilaç adayları bulmayı amaçladık. 6 numaralı sülfonamit türevinin hem CA IX hem de CA XII enzimlerinin aktif bölgelerine sırasıyla -7,44 kcal/mol ve - 6,39 kcal/mol enerji ile referans molekül asetazolamitin (AZM) bağlanmasına en yakın şekilde bağlandığını bulduk. Ayrıca çalışmada kullanılan tüm bileşiklerin ilaç benzeri özelliklerle uyumluluğu ADME yöntemi kullanılarak araştırılmıştır. Sonuç olarak, 1-9 olarak adlandırılmış sülfonamit türevlerinin genel olarak bir ilacın karakteristik özelliklerine (fizikokimyasal ve yapısal özellikler) ve oral biyoyararlanıma sahip olduğu söylenebilir.

Kaynakça

  • [1] Andreucci, E., Ruzzolini, J., Peppicelli, S., Bianchini, F., Laurenzana, A., Carta, F., Supuran, C.T., Caalorini, L., The carbonic anhydrase IX inhibitor SLC-0111 sensitises cancer cells to conventional chemotherapy, Journal of Enzyme Inhibition and Medicinal Chemistry, 34(1), 117-123, 2019.
  • [2] Supuran, C.T., Scozzafava, A., Carbonic anhydrase inhibitors and their therapeutic potential, Expert Opinion on Therapeutic Patents, 10(5), 575-600, 2000.
  • [3] Supuran, C.T., Structure and function of carbonic anhydrases, Biochemical Journal, 473, 2023–2032, 2016.
  • [4] Alterio, V., Hilvo, M., Di Fiore, A., Supuran, C.T., Pan, P., Parkkila, S., Scaloni, A., et al., Crystal structure of the catalytic domain of the tumor-associated human carbonic anhydrase IX, PNAS, 106(38), 16233-16238, 2009.
  • [5] Chegwidden, W.R., Carter, N.D., Edwards Y.H., The carbonic anhydrases, Birkhauser, Boston, 2000.
  • [6] Sly, W.S., Hu P.Y., Human carbonic anhydrases and carbonic anhydrase deficiencies, Annual Review of Biochemistry, 64, 375-401, 1995.
  • [7] Supuran, C.T., Scozzafava, A., Carbonic Anhydrase Inhibitors, Current Medicinal Chemistry, 363(1), 61-97, 2001.
  • [8] Supuran, C.T., Scozzafava, A., Carbonic anhydrases as targets for medicinal chemistry, Bioorganic & Medicinal Chemistry, 15, 4336–4350, 2007.
  • [9] Stadie, W.C., O’Brien, H., The catalytic of the hydration of carbon dioxide and dehydration of carbonic acid by an enzyme isolated from red blood cells, Journal of Biological Chemistry, 103, 521–529, 1933.
  • [10] Wassel, M.M.S., Ragab, A. et al., Novel adamantine-pyrazole and hydrazine hybridized: design, synthesis, cytotoxic evaluation, SAR study and molecular docking simulation as carbonic anhydrase inhibitors, Journal of Molecular Structure, 1223, 128966, 2021.
  • [11] Svastová, E., Hulíková, A., Rafajová, M., Zat’Ovicˇová, M., Gibadulinová, A., Casini, A., Cecchi, A., Scozzafava, A., Supuran, C.T., Pastorek, J., et al., Hypoxia activates the capacity of tumor-associated carbonic anhydrase IX to acidify extracellular pH, FEBS Letters, 577, 439– 445, 2004. [12] Koyuncu, I., Temiz, E., Durgun, M., Kocyigit, A., Yuksekdag, O., Supuran, C.T., Intracellular pH-mediated induction of apoptosis in HeLa cells by a sulfonamide carbonic anhydrase inhibitor, International Journal of Biological Macromolecules, 2022. [13] Temiz, E., Koyuncu, I., Durgun, M., Caglayan, M., Gonel, A., Güler, E. M., Kocyigit, Supuran, C.T., Inhibition of carbonic anhydrase IX promotes apoptosis through intracellular PH level alterations in cervical cancer cells. International Journal of Molecular Sciences, 22(11), 6098, 2021.
  • [14] Durgun, M., Turkmen, H., Zengin, G., Zengin, H., Koyunsever, M., Koyuncu, I., Synthesis, characterization, in vitro cytotoxicity and antimicrobial investigation and evaluation of physicochemical properties of novel 4-(2-methylacetamide) benzenesulfonamide derivatives, Bioorganic Chemistry, 70, 163-172, 2017.
  • [15] Chohan, Z.H., Hassan, M., Khan, K.M., Supuran, C.T., In-vitro antibacterial, antifungal and cytotoxic properties of sulfonamide derived Schiff’s bases and their metal complexes, Journal of Enzyme Inhibition and Medicinal Chemistry, 20(2), 183-188, 2004.
  • [16] Connor, E.E., Sulfonamide antibiotics, Primary Care Update for OB/GYNS, 5(1), 32- 35, 1998.
  • [17] Turkmen, H., Zengin, G., Buyukkircali, B., Synthesis of sulfonamide derivatives and investigation of in vitro inhibitory activities and antimicrobial and physical properties, Bioorganic Chemistry, 39(3), 114-119, 2011.
  • [18] Durgun, M., Zengin, G., Zengin, H., Koyuncu, I., Turkoglu, S., Sonmez, H., Kuru, A., Synthesis, characterization, cytotoxicity evaluation and physicochemical properties of some novel N4-substituted aminobenzenesulfonamides, Indian Journal of Chemistry, 60B, 888-900, 2021.
  • [19] Morris, G.M. et al., Auto dock 4 and auto dock tools 4: automated docking with selective receptor flexibility, Journal of Computational Chemistry, 30, 2785–91, 2009.
  • [20] Hanwell, M.D., Curtis, D.E., Lonie, D.C., Vandermeersch, T., Zurek, E., Hutchison, G.R., Avogadro: an advanced semantic chemical editor, visualization, and analysis platform, Journal of Cheminformatics, 4, 17, 2012.
  • [21] Daina, A., Michielin, O., Zoete, V., SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules, Scientific Reports, 7, 42717, 2017.
  • [22] Mishra, S., Dahima, R., In-vitro ADME studies of TUG-891, a GPR-120 inhibitor using Swiss ADME predictor, Journal of Drug Delivery and Therapeutics, 9(2-s), 266-369, 2019.
  • [23] Farzam, K., Abdullah, M., Acetazolamide. StatPearls Publishing, Treasure Island (FL), 2022.
  • [24] Opavsky, R., Pastorekova, S., Zelnık, V., Gibadulinova, A., Stanbridge, E.J., Zavada, J., Kettmann, R., Pastorek, J., Human MN/CA9 gene, a novel member of the carbonic anhydrase family: structure and exon to protein domain relationships, Genomics, 33, 480–487, 1996.
  • [25] Hilvo, M., Baranauskiene, L., Salzano, A.M., Scaloni, A., Matulis, D., Innocenti, A., Scozzafava, A., Monti, S.M., Di Fiore, A., De Simone, G., Lindfors, M., Janis, J., Valjakka, J., Pastorekova, S., Pastorek, J., Kulomaa, M.S., Nordlund, H.R., Supuran, C.T., Parkkila, S., Biochemical characterization of CA IX, one of the most active carbonic anhydrase isozymes. Journal of Biological Chemistry, 283, 27799–27809, 2008.
  • [26] Boyluğ, Z.E., Yoğunluk Fonksiyonel Teori Temelli Kantitatif Yapi-Etki Analizleri (QSAR): Kumarin Moleküllerinin Karbonik Anhidraz Enzimine Karşi İnhibisyon Etkisinin Modellenmesi. MSc Thesis, Aksaray University, Aksaray, Turkey, 2016.
  • [27] Supuran, C.T., Scozzafava, A., Casini, A., Carbonic anhydrase inhibitors, Medicinal Research Reviews, 23(2), 146–189, 2003.
  • [28] Stams, T., Christianson, D.W., In the carbonic anhydrases. new horizons; Chegwidden, W.R., Carter, N.D., Edwards, Y.H., Eds. Birkhaüser Verlag: Basel, Switzerland, 159p., 2000.
  • [29] Lindahl, M., Vidgren, J., Eriksson, E., Habash, J., Harrop, S., Helliwell, J., Liljas, A., Lindeskog, M., Walker, N., In Carbonic Anhydrase: From Biochemistry and Genetics to Physiology and Clinical Medicine, Botre, F., Gros, G., Storey, B.T., Eds. VCH: Weinheim, Germany, 111p., 1991.
  • [30] Özensoy, Ö., Kanser ile ilişkili Karbon Anhidraz IX ve XII izoenzimlerinin (CA-IX, CA-XII) ekspresyonu, saflaştırılması ve bazı bileşiklere karşı inhibisyon etkilerinin araştırılması, PhD Thesis, Balıkesir University, Balıkesir, Turkey, 2006.
  • [31] Eckert, A.W., Lautner, M.H., Schutze, A., Bolte, K., Bache, M., Kappler, M., Schubert, J., Taubert, H., Bilkenroth, U., Co-expression of Hif1alpha and CA IX is associated with poor prognosis in oral squamous cell carcinoma patients, Journal of Oral Pathology and Medicine, 39, 313–317, 2010.
Toplam 29 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Bölüm Kimya
Yazarlar

Nuri Yorulmaz 0000-0003-4959-2302

Hilal Öztürk 0000-0003-0079-5184

Mustafa Durgun 0000-0003-3012-7582

Yayımlanma Tarihi 30 Haziran 2022
Gönderilme Tarihi 22 Mart 2022
Kabul Tarihi 29 Mayıs 2022
Yayımlandığı Sayı Yıl 2022 Cilt: 12 Sayı: 1

Kaynak Göster

APA Yorulmaz, N., Öztürk, H., & Durgun, M. (2022). Evaluation of Some Sulfonamide Derivatives as a Potential Inhibitors of The Carbonic Anhydrase IX/XII by ADME and Molecular Docking Method. Adıyaman University Journal of Science, 12(1), 88-105. https://doi.org/10.37094/adyujsci.1091227
AMA Yorulmaz N, Öztürk H, Durgun M. Evaluation of Some Sulfonamide Derivatives as a Potential Inhibitors of The Carbonic Anhydrase IX/XII by ADME and Molecular Docking Method. ADYU J SCI. Haziran 2022;12(1):88-105. doi:10.37094/adyujsci.1091227
Chicago Yorulmaz, Nuri, Hilal Öztürk, ve Mustafa Durgun. “Evaluation of Some Sulfonamide Derivatives As a Potential Inhibitors of The Carbonic Anhydrase IX/XII by ADME and Molecular Docking Method”. Adıyaman University Journal of Science 12, sy. 1 (Haziran 2022): 88-105. https://doi.org/10.37094/adyujsci.1091227.
EndNote Yorulmaz N, Öztürk H, Durgun M (01 Haziran 2022) Evaluation of Some Sulfonamide Derivatives as a Potential Inhibitors of The Carbonic Anhydrase IX/XII by ADME and Molecular Docking Method. Adıyaman University Journal of Science 12 1 88–105.
IEEE N. Yorulmaz, H. Öztürk, ve M. Durgun, “Evaluation of Some Sulfonamide Derivatives as a Potential Inhibitors of The Carbonic Anhydrase IX/XII by ADME and Molecular Docking Method”, ADYU J SCI, c. 12, sy. 1, ss. 88–105, 2022, doi: 10.37094/adyujsci.1091227.
ISNAD Yorulmaz, Nuri vd. “Evaluation of Some Sulfonamide Derivatives As a Potential Inhibitors of The Carbonic Anhydrase IX/XII by ADME and Molecular Docking Method”. Adıyaman University Journal of Science 12/1 (Haziran 2022), 88-105. https://doi.org/10.37094/adyujsci.1091227.
JAMA Yorulmaz N, Öztürk H, Durgun M. Evaluation of Some Sulfonamide Derivatives as a Potential Inhibitors of The Carbonic Anhydrase IX/XII by ADME and Molecular Docking Method. ADYU J SCI. 2022;12:88–105.
MLA Yorulmaz, Nuri vd. “Evaluation of Some Sulfonamide Derivatives As a Potential Inhibitors of The Carbonic Anhydrase IX/XII by ADME and Molecular Docking Method”. Adıyaman University Journal of Science, c. 12, sy. 1, 2022, ss. 88-105, doi:10.37094/adyujsci.1091227.
Vancouver Yorulmaz N, Öztürk H, Durgun M. Evaluation of Some Sulfonamide Derivatives as a Potential Inhibitors of The Carbonic Anhydrase IX/XII by ADME and Molecular Docking Method. ADYU J SCI. 2022;12(1):88-105.

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