Molecular Docking Analysis Of N-[2-(3-Methylthio(1,2,4-Thiadiazol-5-Ylthio))Acetyl] Benzamide Molecule With Integrin And DNA

Year 2021, Volume: 6 Issue: 2, 19 - 27, 31.12.2021

A. Demet Demirag , Sefa Çelik , Doğan Özen Ayşen Özel , Sevim Akyüz

Abstract

The most stable structure of the N-[2-(3-Methylthio(1,2,4-thiadiazol-5-ylthio))acetyl] benzamide molecule (C12H11N3O2S3) have been determined by conformational analyses using semi-experimental AM1 calculations. The obtained most stable conformation has been used as the initial data of N-[2-(3-Methylthio(1,2,4-thiadiazol-5-ylthio))acetyl] benzamide in molecular docking analysis. Molecular docking studies of the title molecule with DNA and target protein α5β1 integrin revealed the binding affinities as ΔG = -7.4 and -7.7 kcal/mol, respectively. The binding sites of the target protein integrin and DNA and the interactions of the ligand-integrin and ligand-DNA complexes have been determined, which play an important role in anticancer studies. The 3D docked structures of the investigated molecule in target molecules and the interacted groups of ligand receptor complexes were calculated and shown in figures.

Keywords

Benzamide Molecule, Target Protein Integrin, Molecular Docking, DNA, Anticancer

Supporting Institution

IOCENS Gümüşhane University International Online Conference on ENGINEERING and NATURAL SCIENCES

N-[2-(3-Metiltiyo(1,2,4-Tiyadiazol-5-yltiyo))asetil]benzamid Molekülünün İntegrin ve DNA ile Moleküler Kenetlenme Analizi

Abstract

N-[2-(3-Metiltiyo(1,2,4-tiyadiazol-5-yltiyo))asetil]benzamid molekülünün (C12H11N3O2S3) en kararlı yapısı yarı deneysel AM1 hesaplamaları kullanılarak konformasyon analizi ile belirlenmiştir. Elde edilen en kararlı konformasyon, moleküler kenetlenme analizinde N-[2-(3-Metiltiyo(1,2,4-tiyadiazol-5-yltiyo))asetil]benzamid molekülünün başlangıç verisi olarak kullanılmıştır. Bu molekülün DNA ve hedef protein α5β1 integrini ile yapılan moleküler kenetlenme çalışmaları sonucunda bağlanma afiniteleri sırasıyla ΔG = -7.4 ve -7.7 kcal/mol olarak bulunmuştur. Antikanser çalışmalarda önemli rol oynayan hedef protein integrin ve DNA'nın bağlanma bölgeleri ve ligand-integrin ve ligand-DNA komplekslerinin etkileşimleri belirlenmiştir. İncelenen molekülün hedef moleküllerdeki 3D kenetlenmiş yapıları ve ligand reseptör komplekslerinin etkileşime giren grupları hesaplanmış ve şekillerde gösterilmiştir.

Keywords

Benzamid Molekül, Hedef Protein İntegrin, DNA, Antikanser, Moleküler Kenetleme

References

• [1] Dikshith, T. S. S. (2013). Hazardous chemicals: safety management and global regulations. CRC press.
• [2] Vincoli, J. W. (1996). Risk management for hazardous chemicals (Vol. 1). CRC Press.
• [3] Penfold, B. R., & White, J. C. (1959). The crystal and molecular structure of benzamide. Acta Crystallographica, 12(2), 130-135.
• [4] Huc, I. (2004). Aromatic oligoamide foldamers. European Journal of Organic Chemistry, 2004(1), 17-29.
• [5] Kwolek, S. L., Morgan, P. W., Schaefgen, J. R., & Gulrich, L. W. (1977). Synthesis, anisotropic solutions, and fibers of poly (1, 4-benzamide). Macromolecules, 10(6), 1390-1396.
• [6] Abe, Y. (2012). Polymer Science: A Comprehensive Reference, Lyotropic Polycondensation including Fibers, 469–495. doi:10.1016/B978-0-444-53349-4.00150-3.
• [7] Asif, M. (2016). Pharmacological potential of benzamide analogues and their uses in medicinal chemistry. Modern Chemistry & Applications, 4(4), 1000194.
• [8] Kreinin, A., Novitski, D., & Weizman, A. (2006). Amisulpride treatment of clozapine-induced hypersalivation in schizophrenia patients: a randomized, double-blind, placebo-controlled cross-over study. International clinical psychopharmacology, 21(2), 99-103.
• [9] Ovdiichuk, O. (2016). New Variety of Pyridine and Pyrazine-Based Arginine Mimics: Synthesis, Structural Study and Preliminary Biological Evaluation (Doctoral dissertation, Université de Lorraine).
• [10] Rouanet, J., Quintana, M., Auzeloux, P., Cachin, F., & Degoul, F. (2021). Benzamide derivative radiotracers targeting melanin for melanoma imaging and therapy: Preclinical/clinical development and combination with other treatments. Pharmacology & Therapeutics, 107829.
• [11] Ren, G., Miao, Z., Liu, H., Jiang, L., Limpa-Amara, N., Mahmood, A & Cheng, Z. (2009). Melanin-targeted preclinical PET imaging of melanoma metastasis. Journal of Nuclear Medicine, 50(10), 1692-1699.
• [12] Yilmaz, S., Ataei, S., & Yildiz, İ. (2020). Molecular docking studies on some benzamide derivatives as topoisomerase inhibitors. Journal of Faculty of Pharmacy of Ankara University, 44(3), 470-480.
• [13] Bishayee, A., & Bhatia, D. (Eds.). (2018). Epigenetics of cancer prevention (Vol. 8). Academic Press.
• [14] Gerson, S. L., Caimi, P. F., William, B. M., & Creger, R. J. (2018). Pharmacology and molecular mechanisms of antineoplastic agents for hematologic malignancies. In Hematology (pp. 849-912). Elsevier.
• [15] Mottamal, M., Zheng, S., Huang, T. L., & Wang, G. (2015). Histone deacetylase inhibitors in clinical studies as templates for new anticancer agents. Molecules, 20(3), 3898-3941.
• [16] Garmpis, N., Damaskos, C., Garmpi, A., Valsami, S., & Dimitroulis, D. (2019). Pharmacoepigenetics of Histone Deacetylase Inhibitors in Cancer. In Pharmacoepigenetics (pp. 501-521). Academic Press.
• [17] Vilwanathan, R., Chidambaram, A., & Chidambaram, R. K. (2019). Pharmacoepigenetics: Novel Mechanistic Insights in Drug Discovery and Development Targeting Chromatin-Modifying Enzymes. In Pharmacoepigenetics (pp. 437-445). Academic Press.
• [18] Tumer, T. B., Onder, F. C., Ipek, H., Gungor, T., Savranoglu, S., Tok, T. T., ... & Ay, M. (2017). Biological evaluation and molecular docking studies of nitro benzamide derivatives with respect to in vitro anti-inflammatory activity. International immunopharmacology, 43, 129-139.
• [19] Martinez-Mayorga, K., Peppard, T. L., López-Vallejo, F., Yongye, A. B., & Medina-Franco, J. L. (2013). Systematic mining of generally recognized as safe (GRAS) flavor chemicals for bioactive compounds. Journal of agricultural and food chemistry, 61(31), 7507-7514.
• [20] 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.
• [21] Devar, M.J.S.;Zoebisch, E.G.; Healy, E.F.; Stewart, J.J.P. (1985). AM1: A new General purposequantum mechanical molecular model. Journal of the American Chemical Society,107, 3902-3909.
• [22] Jurcik, A.; Bednar, D.; Byska, J.; Marques, S.M.; Furmanova, K.; Daniel, L.;... Pavelka, A. (2018). CAVER Analyst 2.0: analysis and visualization of channels and tunnels in protein structures and molecular dynamics trajectories. Bioinformatics, 34, 3586-3588.
• [23] Trott, O.; Olson, A.J. (2010). AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of Computational Chemistry,31, 455-461.
• [24] El-Hashash, M.A.E.M., Salem, M. S., & Al-Mabrook, S.A.M. (2018). Synthesis and anticancer activity of novel quinazolinone and benzamide derivatives. Research on Chemical Intermediates, 44(4), 2545-2559.
• [25] 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.
• [26] 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.
• [27] 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.
• [28] 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.
• [29] Xia, W., & Springer, T. A. (2014). Metal ion and ligand binding of integrin α5β1. Proceedings of the National Academy of Sciences, 111(50), 17863-17868.
• [30] 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.
• [31] 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.
• [32] 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.
• [33] 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.
• [34] 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.
• [35] 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.
• [36] 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.