In-silico screening of 2,3-diphenylquinozaline derivatives as C-met kinase inhibitors

Versions

PDF

Keywords

Anticancer
Quinoxaline
C-met Kinase
Molecular docking
AutoDock

How to Cite

(1)
Yahcoob, N.; Lakshmanan, B.; Achuthanandhan, J.; Balakrishnan, V. In-Silico Screening of 2,3-Diphenylquinozaline Derivatives As C-Met Kinase Inhibitors. J Pharm Chem 2021, 4 (3), 41-45. https://doi.org/10.14805/jphchem.2017.art84.

Abstract

Quinoxaline, an important class of heterocylic compounds drawn greater attention due to their wide spectrum of biological activities. They are considered as an important chemical scaffold for anticancer drug design due to their potential inhibitory activity against C-met tyrosine kinase. C-met kinase inhibitors are a class of small molecules that having therapeutic potential in the treatment of various types of cancers. The present study aims to focus on the chemistry of quinoxaline derivatives, their potential activities against C-met tyrosine kinase, and in-silico screening of designed compounds. A series of twelve compounds were designed and docked against C-met tyrosine kinase for their binding energy. All compounds were found to be interacting well with the protein. Compound NQ1 was found to have good binding energy showing an estimated Ki value of  1.1µm. SAR study indicated the presence of an electron withdrawing substitution on benzilidine phenyl ring of quinoxaline greatly improves its binding interaction with the protein.

PDF

References

Geethavani, M.; Reddy, J. R.; Sathyanarayana, S. Synthesis, Antimicrobial And Wound Healing Activities Of Diphenyl Quinoxaline Derivatives. Int J Pharm Tech 2012, 4 (3), 4700-4710.

Urquiola, C.; Gambino, D.; Cabrera, M.; Lavaggi, M. L.; Cerecetto, H.; González, M.; de Cerain, A. L.; Monge, A.; Costa-Filho, A. J.; Torre, M. H. New copper-based complexes with quinoxaline N 1, N 4-dioxide derivatives, potential antitumoral agents. J Inorg Biochem 2008, 102 (1), 119-126.

https://doi.org/10.1016/j.jinorgbio.2007.07.028

Noolvi, M. N.; Patel, H. M.; Bhardwaj, V.; Chauhan, A. Synthesis and in vitro antitumor activity of substituted quinazoline and quinoxaline derivatives: search for anticancer agent. Eur J Med Chem 2011, 46 (6), 2327-2346.

https://doi.org/10.1016/j.ejmech.2011.03.015

Wagle, S.; Adhikari, A. V.; Kumari, N. S. Synthesis of some new 4-styryltetrazolo [1, 5-a] quinoxaline and 1-substituted-4-styryl [1, 2, 4] triazolo [4, 3-a] quinoxaline derivatives as potent anticonvulsants. Eur J Med Chem 2009, 44 (3), 1135-1143.

https://doi.org/10.1016/j.ejmech.2008.06.006

Vicente, E.; Lima, L. M.; Bongard, E.; Charnaud, S.; Villar, R.; Solano, B.; Burguete, A.; Perez-Silanes, S.; Aldana, I.; Vivas, L. Synthesis and structure–activity relationship of 3-phenylquinoxaline 1, 4-di-N-oxide derivatives as antimalarial agents. Eur J Med Chem 2008, 43 (9), 1903-1910.

https://doi.org/10.1016/j.ejmech.2007.11.024

Burguete, A.; Pontiki, E.; Hadjipavlou-Litina, D.; Villar, R.; Vicente, E.; Solano, B.; Ancizu, S.; Pérez-Silanes, S.; Aldana, I.; Monge, A. Synthesis and anti-inflammatory/antioxidant activities of some new ring substituted 3-phenyl-1-(1, 4-di-N-oxide quinoxalin-2-yl)-2-propen-1-one derivatives and of their 4, 5-dihydro-(1H)-pyrazole analogues. Bioorg Med Chem Lett 2007, 17 (23), 6439-6443.

https://doi.org/10.1016/j.bmcl.2007.10.002

Kumar, A.; Verma, A.; Chawla, G.; Studies, V.; Hamdard, J.; Delhi, N. Synthesis, antiinflammatory and antimicrobial activities of new hydrazone and quinoxaline derivatives. Int J ChemTech Res 2009, 1 (4), 1177-1181.

Budakoti, A.; Bhat, A. R.; Azam, A. Synthesis of new 2-(5-substituted-3-phenyl-2-pyrazolinyl)-1, 3-thiazolino [5, 4-b] quinoxaline derivatives and evaluation of their antiamoebic activity. Eur J Med Chem 2009, 44 (3), 1317-1325.

https://doi.org/10.1016/j.ejmech.2008.02.002

Burguete, A.; Pontiki, E.; Hadjipavlou-Litina, D.; Ancizu, S.; Villar, R.; Solano, B.; Moreno, E.; Torres, E.; Pérez, S.; Aldana, I.; Monge, A. Synthesis and Biological Evaluation of New Quinoxaline Derivatives as Antioxidant and Anti-Inflammatory Agents. Chem Biol Drug Des 2011, 77 (4), 255-267.

https://doi.org/10.1111/j.1747-0285.2011.01076.x

Sarges, R.; Howard, H. R.; Browne, R. G.; Lebel, L. A.; Seymour, P. A.; Koe, B. K. 4-Amino[1,2,4]triazolo[4,3-a]quinoxalines. A novel class of potent adenosine receptor antagonists and potential rapid-onset antidepressants. J Med Chem 1990, 33 (8), 2240-2254.

https://doi.org/10.1021/jm00170a031

Hui, X.; Desrivot, J.; Bories, C.; Loiseau, P. M.; Franck, X.; Hocquemiller, R.; Figadere, B. Synthesis and antiprotozoal activity of some new synthetic substituted quinoxalines. Bioorg Med Chem Lett 2006, 16 (4), 815-820.

https://doi.org/10.1016/j.bmcl.2005.11.025

Jampilek, J. Recent advances in design of potential quinoxaline anti-infectives. Curr Med Chem 2014, 21 (38), 4347-4373.

https://doi.org/10.2174/0929867321666141011194825

Deepika, Y. Design, Synthesis of Novel Quinoxaline Derivatives & Their Antinociceptive Activity. Asian J Pharm Health Sci 2012, 2 (1), 261-265.

Kleim, J. P.; Rösner, M.; Winkler, I.; Paessens, A.; Kirsch, R.; Hsiou, Y.; Arnold, E.; Riess, G. Selective pressure of a quinoxaline nonnucleoside inhibitor of human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) on HIV-1 replication results in the emergence of nucleoside RT-inhibitor-specific (RT Leu-74-->Val or Ile and Val-75-->Leu or Ile) HIV-1 mutants. Proc Natl Acad Sci USA1996,93 (1), 34-38.

https://doi.org/10.1073/pnas.93.1.34

Kohno, T.; Tsuta, K.; Tsuchihara, K.; Nakaoku, T.; Yoh, K.; Goto, K. RET fusion gene: translation to personalized lung cancer therapy. Cancer Sci 2013, 104 (11), 1396-1400.

https://doi.org/10.1111/cas.12275

Kazandjian, D.; Blumenthal, G. M.; Chen, H.-Y.; He, K.; Patel, M.; Justice, R.; Keegan, P.; Pazdur, R. FDA Approval Summary: Crizotinib for the Treatment of Metastatic Non-Small Cell Lung Cancer With Anaplastic Lymphoma Kinase Rearrangements. Oncologist 2014, 19 (10), e5-e11.

https://doi.org/10.1634/theoncologist.2014-0241

Hart, C. D.; De Boer, R. H. Profile of cabozantinib and its potential in the treatment of advanced medullary thyroid cancer. Onco Targets Ther 2013, 6, 1-7. https://doi.org/10.2147/OTT.S27671

Myers, M. R.; He, W.; Hanney, B.; Setzer, N.; Maguire, M. P.; Zulli, A.; Bilder, G.; Galzcinski, H.; Amin, D.; Needle, S. Potent quinoxaline-based inhibitors of PDGF receptor tyrosine kinase activity. Part 1: SAR exploration and effective bioisosteric replacement of a phenyl substituent. Bioorg Med Chem Lett 2003, 13 (18), 3091-3095.

https://doi.org/10.1016/S0960-894X(03)00654-1

He, W.; Myers, M. R.; Hanney, B.; Spada, A. P.; Bilder, G.; Galzcinski, H.; Amin, D.; Needle, S.; Page, K.; Jayyosi, Z. Potent quinoxaline-Based inhibitors of PDGF receptor tyrosine kinase activity. Part 2: the synthesis and biological activities of RPR127963 an orally bioavailable inhibitor. Bioorg Med Chem Lett 2003, 13 (18), 3097-3100.

https://doi.org/10.1016/S0960-894X(03)00655-3

Unzue, A.; Dong, J.; Lafleur, K.; Zhao, H.; Frugier, E.; Caflisch, A.; Nevado, C. Pyrrolo [3, 2-b] quinoxaline derivatives as types i1/2 and ii eph tyrosine kinase inhibitors: structure-based design, synthesis, and in vivo validation. J Med Chem 2014, 57 (15), 6834-6844.

https://doi.org/10.1021/jm5009242

El Newahie, A.; Ismail, N. S.; El Ella, A.; Dalal, A.; Abouzid, K. A. Quinoxalineâ€Based Scaffolds Targeting Tyrosine Kinases and Their Potential Anticancer Activity. Arch Der Pharm 2016, 349 (5), 309-326.

https://doi.org/10.1002/ardp.201500468

Schiering, N.; Knapp, S.; Marconi, M.; Flocco, M. M.; Cui, J.; Perego, R.; Rusconi, L.; Cristiani, C. Crystal structure of the tyrosine kinase domain of the hepatocyte growth factor receptor c-Met and its complex with the microbial alkaloid K-252a. Proc Natl Acad Sci USA 2003, 100 (22), 12654-12659.

https://doi.org/10.1073/pnas.1734128100

Creative Commons License

This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.

Copyright (c) 2017 JOURNAL OF PHARMACEUTICAL CHEMISTRY