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Antikanser Acalabrutinib Molekülünün Konformasyonel, Toksik, Fizikokimyasal ve Moleküler Kenetlenme Analizi

Year 2022, Volume 7, Issue 1, 1 - 9, 30.06.2022

Abstract

Acalabrutinib, Bruton'un tirozin kinaz (BTK) aktivitesinin bir inhibitörüdür ve B hücresi antijen reseptörü (BCR) sinyal yolunun aktivasyonunu önler. Acalabrutinib bu özelliklere sahip olduğu için yakın zamanda bir antikanser ilacı olarak tıbbi kullanım için onaylanmıştır. Biyoaktif bir molekülün konformasyonel özelliklerinin belirlenmesi, biyoaktivitesini ortaya çıkarmak için gereklidir. Bu nedenle öncelikle acalabrutinib'in konformasyonel durumları incelenmiştir. Acalabrutinib molekülünün kararlı yapılarını incelemek için yarı deneysel bir yöntem olan AM1 kullanılmıştır. Acalabrutinib molekülünün en düşük enerjili dokuz konformeri belirlenmiştir ve bağıl enerjileri hesaplanmıştır. Daha sonra acalabrutinib'in en kararlı konformerinin DNA ve integrin ile etkileşimleri kenetlenme simülasyonları ile incelenmiş ve en aktif etkileşim bölgeleri ve bağlanma afiniteleri belirlenmiştir.

References

  • Satterthwaite A.B. Bruton’s Tyrosine Kinase, a Component of B Cell Signaling Pathways, Has Multiple Roles in the Pathogenesis of Lupus, Frontiers in Immunology, 8 (2018) 1-10. Article No 1986.
  • Acalabrutinib Monograph for Professionals, Drugs.com. Retrieved 16 March 2019.
  • Barf, T., Covey, T., Izumi, R., van de Kar, B., Gulrajani, M., van Lith, B., ... & Kaptein, A. (2017). Acalabrutinib (ACP-196): a covalent Bruton tyrosine kinase inhibitor with a differentiated selectivity and in vivo potency profile. Journal of Pharmacology and Experimental Therapeutics, 363(2), 240-252.
  • Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner CM, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014;370(12):1101–10.
  • Cang S, Iragavarapu C, Savooji J, Song Y, Liu D. ABT-199 (venetoclax) and BCL-2 inhibitors in clinical development. J Hematol Oncol. 2015;8(1):129.
  • Novero A, Ravella PM, Chen Y, Dous G, Liu D. Ibrutinib for B cell malignancies. Experimental Hematology & Oncology. 2014;3(1):1–7.
  • Covey T, Barf T, Gulrajani M, Krantz F, van Lith B, Bibikova E, et al. Abstract 2596: ACP-196: a novel covalent Bruton’s tyrosine kinase (Btk) inhibitor with improved selectivity and in vivo target coverage in chronic lymphocytic leukemia (CLL) patients. Cancer Res. 2015;75(15 Supplement):2596.
  • Walter HS, Rule SA, Dyer MJS, Karlin L, Jones C, Cazin B, et al. A phase 1 clinical trial of the selective BTK inhibitor ONO/GS-4059 in relapsed and refractory mature B-cell malignancies. Blood. 2016;127(4):411–9.
  • The New England Journal of Medicine 374;4 nejm.org January 28, 2016.
  • Ferit Avcu, Kll Tedavisinde Gelecek: Hedefe Yönelik Yeni Moleküller XXXIX. Ulusal Hematoloji Kongresi.
  • Treon SP, Tripsas CK, Meid K, Warren D, Varma G, Green R, et al. Ibrutinib in previously treated Waldenstrom’s macroglobulinemia. N Engl J Med. 2015; 372(15):1430–40.
  • Byrd JC, Furman RR, Coutre SE, Flinn IW, Burger JA, Blum KA, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369(1):32–42.
  • Brown JR, Barrientos JC, Barr PM, Flinn IW, Burger JA, Tran A, et al. The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia. Blood. 2015;125(19):2915–22.
  • Burger JA, Tedeschi A, Barr PM, Robak T, Owen C, Ghia P, et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015;373(25):2425–37.
  • https://pubchem.ncbi.nlm.nih.gov/compound/71226662
  • Maddocks KJ, Ruppert AS, Lozanski G, et al. Etiology of ibrutinib therapy dis- continuation and outcomes in patients with chronic lymphocytic leukemia. JAMA Oncol 2015;1:80-7.
  • Jain P, Keating M, Wierda W, et al. Outcomes of patients with chronic lym- phocytic leukemia after discontinuing ibrutinib. Blood 2015;125:2062-7. ClinicalTrials.gov number, NCT02477696
  • Shao, Y., Molnar, L. F., Jung, Y., Kussmann, J., Ochsenfeld, C., Brown, S. T., ... & DiStasio Jr, R. A. (2006). Advances in methods and algorithms in a modern quantum chemistry program package. Physical Chemistry Chemical Physics,8(27), 3172-3191.
  • Devar, M.J.S.;Zoebisch, E.G.; Healy, E.F.; Stewart, J.J.P. AM1: A new General purposequantum mechanical molecular model.J. Am. Chem. Soc.1985, 107, 3902-3909.
  • Jurcik, A.; Bednar, D.; Byska, J.; Marques, S.M.; Furmanova, K.; Daniel, L.;... Pavelka, A. CAVER Analyst 2.0: analysis and visualization of channels and tunnels in protein structures and molecular dynamics trajectories. Bioinformatics 2018, 34, 3586-3588.
  • Trott, O.; Olson, A.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading.J. Comput. Chem. 2010,31, 455-461.
  • OSIRIS. (2010).OSIRIS Property Explorer. Actelion Pharmaceuticals Ltd. http://www. https://www.organic-chemistry.org/prog/peo/
  • Drew, H. R., Wing, R. M., Takano, T., Broka, C., Tanaka, S., Itakura, K., &Dickerson, R. E. (1981). Structure of a B-DNA dodecamer:Conformation and dynamics.Proceedings of the National Academy ofSciences,78(4), 2179–2183.
  • Celik, S., Yilmaz, G., Ozel, A. E., & Akyuz, S. (2020). Structural and spectral analysis of anticancer active cyclo (Ala–His) dipeptide. Journal of Biomolecular Structure and Dynamics, 1-13.
  • Akalin, E., Celik, S., & Akyuz, S. (2020). Molecular Modeling, Dimer Calculations, Vibrational Spectra, and Molecular Docking Studies of 5-Chlorouracil. Journal of Applied Spectroscopy, 86(6), 975-985.
  • Arif, R., Rana, M., Yasmeen, S., Khan, M. S., Abid, M., & Khan, M. S. (2020). Facile synthesis of chalcone derivatives as antibacterial agents: Synthesis, DNA binding, molecular docking, DFT and antioxidant studies. Journal of Molecular Structure, 1208, 127905.
  • W. Xia, T.A. Springer, Metal ion and ligand binding of Integrin α5β1, PNAS 111 (2014) 17863-17868, http://doi.org/10.1073/pnas.1420645111.
  • Gasymov, O. K., Celik, S., Agaeva, G., Akyuz, S., Kecel-Gunduz, S., Qocayev, N. M., ... & Aliyev, J. A. (2021). Evaluation of anti-cancer and anti-covid-19 properties of cationic pentapeptide Glu-Gln-Arg-Pro-Arg, from rice bran protein and its d-isomer analogs through molecular docking simulations. Journal of Molecular Graphics and Modelling, 108, 107999.
  • Wang, Z., Wang, X., Li, Y., Lei, T., Wang, E., Li, D., ... & Hou, T. (2019). farPPI: a webserver for accurate prediction of protein-ligand binding structures for small-molecule PPI inhibitors by MM/PB (GB) SA methods. Bioinformatics, 35(10), 1777-1779.
  • Hao, G. F., Jiang, W., Ye, Y. N., Wu, F. X., Zhu, X. L., Guo, F. B., & Yang, G. F. (2016). ACFIS: a web server for fragment-based drug discovery. Nucleic acids research, 44(W1), W550-W556.
  • Hao, G. F., Wang, F., Li, H., Zhu, X. L., Yang, W. C., Huang, L. S., ... & Yang, G. F. (2012). Computational discovery of picomolar Q o site inhibitors of cytochrome bc 1 complex. Journal of the American Chemical Society, 134(27), 11168-11176.
  • Yang, J. F., Wang, F., Jiang, W., Zhou, G. Y., Li, C. Z., Zhu, X. L., ... & Yang, G. F. (2018). PADFrag: a database built for the exploration of bioactive fragment space for drug discovery. Journal of chemical information and modeling, 58(9), 1725-1730.
  • Cheron, N., Jasty, N., & Shakhnovich, E. I. (2016). OpenGrowth: an automated and rational algorithm for finding new protein ligands. Journal of medicinal chemistry, 59(9), 4171-4188.
  • Wang, E., Sun, H., Wang, J., Wang, Z., Liu, H., Zhang, J. Z., & Hou, T. (2019). End-point binding free energy calculation with MM/PBSA and MM/GBSA: strategies and applications in drug design. Chemical reviews, 119(16), 9478-9508.

Conformational, Toxic, Physicochemical and Molecular Docking Analysis of the Anticancer Acalabrutinib Molecule

Year 2022, Volume 7, Issue 1, 1 - 9, 30.06.2022

Abstract

Acalabrutinib is an inhibitor of Bruton's tyrosine kinase (BTK) activity and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway. For having these properties acalabrutinib recently was approved for medical use as an anticancer drug. Determining the conformational properties of a bioactive molecule is necessary to reveal its bioactivity. For this reason, the conformational states of the acalabrutinib were examined first. The AM1, a semi-experimental method, was used to examine the stable conformations of the acalabrutinib molecule. Nine lowest energy conformers of the acalabrutinib molecule were determined and their relative energies were calculated. Afterwards, the interactions of the most stable conformer of acalabrutinib with DNA and integrin were examined by docking simulations, and the most active interaction sites and binding affinities were determined.

References

  • Satterthwaite A.B. Bruton’s Tyrosine Kinase, a Component of B Cell Signaling Pathways, Has Multiple Roles in the Pathogenesis of Lupus, Frontiers in Immunology, 8 (2018) 1-10. Article No 1986.
  • Acalabrutinib Monograph for Professionals, Drugs.com. Retrieved 16 March 2019.
  • Barf, T., Covey, T., Izumi, R., van de Kar, B., Gulrajani, M., van Lith, B., ... & Kaptein, A. (2017). Acalabrutinib (ACP-196): a covalent Bruton tyrosine kinase inhibitor with a differentiated selectivity and in vivo potency profile. Journal of Pharmacology and Experimental Therapeutics, 363(2), 240-252.
  • Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner CM, et al. Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med. 2014;370(12):1101–10.
  • Cang S, Iragavarapu C, Savooji J, Song Y, Liu D. ABT-199 (venetoclax) and BCL-2 inhibitors in clinical development. J Hematol Oncol. 2015;8(1):129.
  • Novero A, Ravella PM, Chen Y, Dous G, Liu D. Ibrutinib for B cell malignancies. Experimental Hematology & Oncology. 2014;3(1):1–7.
  • Covey T, Barf T, Gulrajani M, Krantz F, van Lith B, Bibikova E, et al. Abstract 2596: ACP-196: a novel covalent Bruton’s tyrosine kinase (Btk) inhibitor with improved selectivity and in vivo target coverage in chronic lymphocytic leukemia (CLL) patients. Cancer Res. 2015;75(15 Supplement):2596.
  • Walter HS, Rule SA, Dyer MJS, Karlin L, Jones C, Cazin B, et al. A phase 1 clinical trial of the selective BTK inhibitor ONO/GS-4059 in relapsed and refractory mature B-cell malignancies. Blood. 2016;127(4):411–9.
  • The New England Journal of Medicine 374;4 nejm.org January 28, 2016.
  • Ferit Avcu, Kll Tedavisinde Gelecek: Hedefe Yönelik Yeni Moleküller XXXIX. Ulusal Hematoloji Kongresi.
  • Treon SP, Tripsas CK, Meid K, Warren D, Varma G, Green R, et al. Ibrutinib in previously treated Waldenstrom’s macroglobulinemia. N Engl J Med. 2015; 372(15):1430–40.
  • Byrd JC, Furman RR, Coutre SE, Flinn IW, Burger JA, Blum KA, et al. Targeting BTK with ibrutinib in relapsed chronic lymphocytic leukemia. N Engl J Med. 2013;369(1):32–42.
  • Brown JR, Barrientos JC, Barr PM, Flinn IW, Burger JA, Tran A, et al. The Bruton tyrosine kinase inhibitor ibrutinib with chemoimmunotherapy in patients with chronic lymphocytic leukemia. Blood. 2015;125(19):2915–22.
  • Burger JA, Tedeschi A, Barr PM, Robak T, Owen C, Ghia P, et al. Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med. 2015;373(25):2425–37.
  • https://pubchem.ncbi.nlm.nih.gov/compound/71226662
  • Maddocks KJ, Ruppert AS, Lozanski G, et al. Etiology of ibrutinib therapy dis- continuation and outcomes in patients with chronic lymphocytic leukemia. JAMA Oncol 2015;1:80-7.
  • Jain P, Keating M, Wierda W, et al. Outcomes of patients with chronic lym- phocytic leukemia after discontinuing ibrutinib. Blood 2015;125:2062-7. ClinicalTrials.gov number, NCT02477696
  • Shao, Y., Molnar, L. F., Jung, Y., Kussmann, J., Ochsenfeld, C., Brown, S. T., ... & DiStasio Jr, R. A. (2006). Advances in methods and algorithms in a modern quantum chemistry program package. Physical Chemistry Chemical Physics,8(27), 3172-3191.
  • Devar, M.J.S.;Zoebisch, E.G.; Healy, E.F.; Stewart, J.J.P. AM1: A new General purposequantum mechanical molecular model.J. Am. Chem. Soc.1985, 107, 3902-3909.
  • Jurcik, A.; Bednar, D.; Byska, J.; Marques, S.M.; Furmanova, K.; Daniel, L.;... Pavelka, A. CAVER Analyst 2.0: analysis and visualization of channels and tunnels in protein structures and molecular dynamics trajectories. Bioinformatics 2018, 34, 3586-3588.
  • Trott, O.; Olson, A.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading.J. Comput. Chem. 2010,31, 455-461.
  • OSIRIS. (2010).OSIRIS Property Explorer. Actelion Pharmaceuticals Ltd. http://www. https://www.organic-chemistry.org/prog/peo/
  • Drew, H. R., Wing, R. M., Takano, T., Broka, C., Tanaka, S., Itakura, K., &Dickerson, R. E. (1981). Structure of a B-DNA dodecamer:Conformation and dynamics.Proceedings of the National Academy ofSciences,78(4), 2179–2183.
  • Celik, S., Yilmaz, G., Ozel, A. E., & Akyuz, S. (2020). Structural and spectral analysis of anticancer active cyclo (Ala–His) dipeptide. Journal of Biomolecular Structure and Dynamics, 1-13.
  • Akalin, E., Celik, S., & Akyuz, S. (2020). Molecular Modeling, Dimer Calculations, Vibrational Spectra, and Molecular Docking Studies of 5-Chlorouracil. Journal of Applied Spectroscopy, 86(6), 975-985.
  • Arif, R., Rana, M., Yasmeen, S., Khan, M. S., Abid, M., & Khan, M. S. (2020). Facile synthesis of chalcone derivatives as antibacterial agents: Synthesis, DNA binding, molecular docking, DFT and antioxidant studies. Journal of Molecular Structure, 1208, 127905.
  • W. Xia, T.A. Springer, Metal ion and ligand binding of Integrin α5β1, PNAS 111 (2014) 17863-17868, http://doi.org/10.1073/pnas.1420645111.
  • Gasymov, O. K., Celik, S., Agaeva, G., Akyuz, S., Kecel-Gunduz, S., Qocayev, N. M., ... & Aliyev, J. A. (2021). Evaluation of anti-cancer and anti-covid-19 properties of cationic pentapeptide Glu-Gln-Arg-Pro-Arg, from rice bran protein and its d-isomer analogs through molecular docking simulations. Journal of Molecular Graphics and Modelling, 108, 107999.
  • Wang, Z., Wang, X., Li, Y., Lei, T., Wang, E., Li, D., ... & Hou, T. (2019). farPPI: a webserver for accurate prediction of protein-ligand binding structures for small-molecule PPI inhibitors by MM/PB (GB) SA methods. Bioinformatics, 35(10), 1777-1779.
  • Hao, G. F., Jiang, W., Ye, Y. N., Wu, F. X., Zhu, X. L., Guo, F. B., & Yang, G. F. (2016). ACFIS: a web server for fragment-based drug discovery. Nucleic acids research, 44(W1), W550-W556.
  • Hao, G. F., Wang, F., Li, H., Zhu, X. L., Yang, W. C., Huang, L. S., ... & Yang, G. F. (2012). Computational discovery of picomolar Q o site inhibitors of cytochrome bc 1 complex. Journal of the American Chemical Society, 134(27), 11168-11176.
  • Yang, J. F., Wang, F., Jiang, W., Zhou, G. Y., Li, C. Z., Zhu, X. L., ... & Yang, G. F. (2018). PADFrag: a database built for the exploration of bioactive fragment space for drug discovery. Journal of chemical information and modeling, 58(9), 1725-1730.
  • Cheron, N., Jasty, N., & Shakhnovich, E. I. (2016). OpenGrowth: an automated and rational algorithm for finding new protein ligands. Journal of medicinal chemistry, 59(9), 4171-4188.
  • Wang, E., Sun, H., Wang, J., Wang, Z., Liu, H., Zhang, J. Z., & Hou, T. (2019). End-point binding free energy calculation with MM/PBSA and MM/GBSA: strategies and applications in drug design. Chemical reviews, 119(16), 9478-9508.

Details

Primary Language English
Subjects Engineering, Engineering, Chemical
Journal Section Research Article
Authors

Sefa ÇELİK
İSTANBUL ÜNİVERSİTESİ, FEN FAKÜLTESİ
0000-0001-6216-1297
Türkiye


A. Demet DEMİRAG (Primary Author)
YEDITEPE UNIVERSITY
0000-0002-9609-9150
Türkiye


Samet ARSLAN
YEDİTEPE ÜNİVERSİTESİ, MESLEK YÜKSEKOKULU
0000-0003-2164-3905
Türkiye


Ayşen ÖZEL
İSTANBUL ÜNİVERSİTESİ, FEN FAKÜLTESİ
0000-0002-8680-8830
Türkiye


Sevim AKYÜZ
İSTANBUL KÜLTÜR ÜNİVERSİTESİ, FEN-EDEBİYAT FAKÜLTESİ
0000-0003-3313-6927
Türkiye

Supporting Institution IOCENS Gümüşhane University International Online Conference on ENGINEERING and NATURAL SCIENCES
Early Pub Date March 3, 2022
Publication Date June 30, 2022
Published in Issue Year 2022, Volume 7, Issue 1

Cite

Bibtex @research article { ojn1004702, journal = {Open Journal of Nano}, issn = {}, eissn = {2147-0081}, address = {Sakarya Üniversitesi Fatih Mah. Eşit Sok. No:7/A -11 54580 - Arifiye / SAKARYA}, publisher = {Mustafa CAN}, year = {2022}, volume = {7}, pages = {1 - 9}, doi = {}, title = {Conformational, Toxic, Physicochemical and Molecular Docking Analysis of the Anticancer Acalabrutinib Molecule}, key = {cite}, author = {Çelik, Sefa and Demirag, A. Demet and Arslan, Samet and Özel, Ayşen and Akyüz, Sevim} }
APA Çelik, S. , Demirag, A. D. , Arslan, S. , Özel, A. & Akyüz, S. (2022). Conformational, Toxic, Physicochemical and Molecular Docking Analysis of the Anticancer Acalabrutinib Molecule . Open Journal of Nano , 7 (1) , 1-9 . Retrieved from https://dergipark.org.tr/en/pub/ojn/issue/66849/1004702
MLA Çelik, S. , Demirag, A. D. , Arslan, S. , Özel, A. , Akyüz, S. "Conformational, Toxic, Physicochemical and Molecular Docking Analysis of the Anticancer Acalabrutinib Molecule" . Open Journal of Nano 7 (2022 ): 1-9 <https://dergipark.org.tr/en/pub/ojn/issue/66849/1004702>
Chicago Çelik, S. , Demirag, A. D. , Arslan, S. , Özel, A. , Akyüz, S. "Conformational, Toxic, Physicochemical and Molecular Docking Analysis of the Anticancer Acalabrutinib Molecule". Open Journal of Nano 7 (2022 ): 1-9
RIS TY - JOUR T1 - Conformational, Toxic, Physicochemical and Molecular Docking Analysis of the Anticancer Acalabrutinib Molecule AU - Sefa Çelik , A. Demet Demirag , Samet Arslan , Ayşen Özel , Sevim Akyüz Y1 - 2022 PY - 2022 N1 - DO - T2 - Open Journal of Nano JF - Journal JO - JOR SP - 1 EP - 9 VL - 7 IS - 1 SN - -2147-0081 M3 - UR - Y2 - 2021 ER -
EndNote %0 Open Journal of Nano Conformational, Toxic, Physicochemical and Molecular Docking Analysis of the Anticancer Acalabrutinib Molecule %A Sefa Çelik , A. Demet Demirag , Samet Arslan , Ayşen Özel , Sevim Akyüz %T Conformational, Toxic, Physicochemical and Molecular Docking Analysis of the Anticancer Acalabrutinib Molecule %D 2022 %J Open Journal of Nano %P -2147-0081 %V 7 %N 1 %R %U
ISNAD Çelik, Sefa , Demirag, A. Demet , Arslan, Samet , Özel, Ayşen , Akyüz, Sevim . "Conformational, Toxic, Physicochemical and Molecular Docking Analysis of the Anticancer Acalabrutinib Molecule". Open Journal of Nano 7 / 1 (June 2022): 1-9 .
AMA Çelik S. , Demirag A. D. , Arslan S. , Özel A. , Akyüz S. Conformational, Toxic, Physicochemical and Molecular Docking Analysis of the Anticancer Acalabrutinib Molecule. ojn. 2022; 7(1): 1-9.
Vancouver Çelik S. , Demirag A. D. , Arslan S. , Özel A. , Akyüz S. Conformational, Toxic, Physicochemical and Molecular Docking Analysis of the Anticancer Acalabrutinib Molecule. Open Journal of Nano. 2022; 7(1): 1-9.
IEEE S. Çelik , A. D. Demirag , S. Arslan , A. Özel and S. Akyüz , "Conformational, Toxic, Physicochemical and Molecular Docking Analysis of the Anticancer Acalabrutinib Molecule", Open Journal of Nano, vol. 7, no. 1, pp. 1-9, Jun. 2022

ISSN: 2147-0081
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