Docking and Qsar Studies of Some Quinazolinone Derivatives as Possible Inhibitors of Thyrosine Kinase

Year 2022, Volume: 6 Issue: 2, 1 - 10, 15.12.2022

Fahimeh Ghasemi , Elham Jafari , Mahmoud Mırzaeı , Karim Mahnam

Abstract

Quinazolinones are bicyclic fused heterocyclics that have been shown cytotoxic effects through different mechanisms inparticular thyrozin kinase enzyme inhibition. Based on this, a series of quinazolinone derivatives were subjected to a quantitative structure activity relationship (QSAR) analysis, by using statistical tool, such as principal components analysis (PCA) and genetic algorithm (G.A). It was shown that GA_PLS is reliable to predict activities of new design compounds. Besides, the compounds were docked into the active site of the protein thyrozin kinase (PDB entry code:1M17) to identify the binding interactions. Among the thirty two studied compounds, five compounds showed convenient inhibitory effect. The most active compound of the studied derivatives , Q19, had a ∆Gbind of-9.52kcal/mol.

Keywords

Quinazolinone;, Thyrosin kinase, GA_PLS

References

• [1] S. Ranjbar, N. Edraki, M. Khoshneviszadeh, A. Foroumadi, R. Miri, M. Khoshneviszadeh.. Design, synthesis, cytotoxicity evaluation and docking studies of 1, 2, 4-triazine derivatives bearing different arylidene-hydrazinyl moieties as potential mTOR inhibitors, Res. Pharm. sci. 13(1), (2018) 1-11.
• [2] X. Qin, Z .Li, L. Yang, P. Liu, L. Hu, C. Zeng, Z. Pan. Discovery of new [1, 4] dioxino [2, 3-f] quinazoline-based inhibitors of EGFR including the T790M/L858R mutant, Bioorg & Med Chem. 24 (2016) 2871-2881.
• [3] X. Qin, Y. Lv, P. Liu, Z .Li, L. Hu, C. Zeng, L. Yang. Novel morpholin-3-one fused quinazoline derivatives as EGFR tyrosine kinase inhibitors Bioorg & Medl Chem Lett. 26 (2016) 1571-5.
• [4] A.S. Shaw, A.P. Kornev, J. Hu, L.G. Ahuja, S.S. Taylor. Kinases and pseudokinases: lessons from RAF. Mol. Cell. Biol.34 (2014) 1538-1546.
• [5] G. Vaseghi, E. Jafari, F. Hassanzadeh, S. Haghjooy-Javanmard, N. Dana, M. Rafieian-Kopaei.Cytotoxic evaluation of some fused pyridazino-and pyrrolo-quinazolinones derivatives on melanoma and prostate cell lines. Adv. Biomed. Res.6 ( 2017):1-4.
• [6] T. Elavarasan, D. Bhakiarajand, M. Gopalakrishnan. Antimicrobial screening and molecular docking studies of some novel triazoloquinazolinone derivatives. Der Pharm. Chem.6 (2014) 391-400.
• [7] E. Jafari, G.A. Khodarahmi, F. Hassanzadeh, G.H. Hakimelahi, F. Tsai. Synthesis of some new tricyclic 4 (3H)-quinazolinone derivatives. Res. Pharm. Scie .6 (2011) 93-100.
• [8] M.A. Mohamed, H.M. Ghanem, N.F .Abd El-Ghaffar, S.S .Mohamed. Biological evaluation and molecular docking of substituted quinazolinones as antimicrobial agents. Aust J Basic Appl Sci. 7 (2013) 263-274.
• [9] G.A. Khodarahmi, M.R. Khajouei, G.H. Hakimelahi, D. Abedi, E. Jafari, F. Hassanzadeh Antibacterial, antifungal and cytotoxic evaluation of some new 2, 3-disubstituted 4 (3H)-quinazolinone derivatives. Res. Pharm. Scie 7 (2012) 151-158.
• [10] F. Hassanzadeh, M.R. Khajouei, G.H. Hakimelahi, E. Jafari, G.A. Khodarahmi. Synthesis of some new 2, 3-disubstituted-4 (3H) quinazolinone derivatives. Res. Pharm. Scie 7 (2012) 23-30.
• [11] G.A. Khodarahmi, E. Jafari, G.H. Hakimelahi, D. Abedi, M.R. Khajouei, F. HassanzadeSynthesis of some new quinazolinone derivatives and evaluation of their antimicrobial activities. Iran. J. Pharm. Sci. 11.( 2012)789-797.
• [12] E. Jafari, M.R. Khajouei, F. Hassanzadeh, G.H. Hakimelahi, G.A. Khodarahmi.. Quinazolinone and quinazoline derivatives: recent structures with potent antimicrobial and cytotoxic activities Res. Pharm. Scie11 (2016) 1-14.
• [13] M.E. Sahu, A.G. Nerkar. In silico screening, synthesis and in vitro evaluation of some quinazolinone derivatives as dihydrofolate reductase inhibitors for anticancer activity: Part-I. International . Int. J Pharm & . Pharm. Sci 6 (2014) 193-199.
• [14] V. Srivastava, S.P. Gupta, M.I. Siddiqi, B.N. Mishra. Molecular docking studies on quinazoline antifolate derivatives as human thymidylate synthase inhibitors. Bioinformation. 4 (2010) 357-365.
• [15] P.M. Chandrika, T. Yakaiah, B. Narsaiah, V. Sridhar, G .Venugopal, J .Venkateshwara rao, et al.. Synthesis leading to novel 2, 4, 6-trisubstituted quinazoline derivatives, their antibacterial and cytotoxic activity against THP-1, HL-60 and A375 cell line. Indian J. Chem. 48B( 2009) 840-847.
• [16] K. Srivalli, K. Satish. Synthesis, In Vitro Evaluation of Some Novel Quinazolin-4 (3H)-one Derivatives as Anti-Tumor Agents. Chem. Sci. Trans. 1( 2012) 624-631.
• [17] L. Hosseinzadeh, A. Aliabadi, M. Rahnama, H.M. Sadeghi, M.R .Khajouei Synthesis and cytotoxic evaluation of some new 3-(2-(2-phenylthiazol-4-yl) ethyl)-quinazolin-4 (3H) one derivatives with potential anticancer effects. Res. Pharm. Scie 12(2017) 290-298.
• [18] F. Hassanzadeh, E. Jafari, G.H. Hakimelahi, M.R. Khajouei, M. Jalali, G.A. Khodarahmi. A. Antibacterial, antifungal and cytotoxic evaluation of some new quinazolinone derivatives. Res. Pharm. Scie7 .( 2012) 87-94.
• [19] F. Hassanzadeh, H. Sadeghi-Aliabadi, E. Jafari, A. Sharifzadeh, N. Dana. Synthesis and cytotoxic evaluation of some quinazolinone-5-(4-chlorophenyl) 1, 3, 4-oxadiazole conjugates. Res. Pharm. Scie,14 ( 2019) 408-413.
• [20] F. Hassanzadeh, H. Sadeghi-Aliabadi, S. Nikooei, E. Jafari, G. Vaseghi. Synthesis and cytotoxic evaluation of some derivatives of triazole-quinazolinone hybrids. Res. Pharm. Scie 14 (2019) 130-137.
• [21] F. Ghasemi, A. Mehridehnavi, A. Perez-Garrido, H .Perez-Sanchez,, Neural network and deep-learning algorithms used in QSAR studies: merits and drawbacks, Drug Discov. 23 (2018)1784-1790.
• [22] T. Mostashari-Rad, R. Arian, H. Sadri, A. Mehridehnavi, M. Mokhtari, F. Ghasemi, A. Fassihi, Study of CXCR4 chemokine receptor inhibitors using QSPR and molecular docking methodologies, J. Theor. Comput. Chem. 18 ( 2019)
• [23] F. Ghasemi, A. Mehri, J. Peña-García, H. den-Haan, A. Pérez-Garrido, A. Fassihi, H. Péréz-Sánchez, Improving Activity Prediction of Adenosine A2B Receptor Antagonists by Nonlinear Models, Int. Conf. Bioinform. Biomed. Eng.(2015) 635-644
• [24] F. Hassanzadeh, E. Jafari, M. Zarabi, G. Khodarahmi, G. Vaseghi Synthesis, cytotoxic evaluation, and molecular docking studies of some new 1, 3, 4-oxadiazole-based compounds. Res. Pharm. Scie.15 (2020) 454-462.
• [25] A Ousaa.QSAR and docking studies on the pyrimidine derivatives analogs with antileishmanial activity. RHAZES: Green. App. Chem.1 (2018) 50-63.
• [26] A.Y. Helali, M.T. Sarg, M.M. Koraa, M.S. El-Zoghbi.,. Utility of 2-methyl-quinazolin-4 (3H)-one in the synthesis of heterocyclic compounds with anticancer activity. Open. J. Medi. Chem 28(2014) 12-37.