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In-silico Drug Design, ADMET Screening, MM-GBSA Binding Free Energy of Some Chalcone Substituted 9-Anilinoacridines as HER2 Inhibitors for Breast Cancer

Received: 23 January 2019     Accepted: 25 February 2019     Published: 18 March 2019
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Abstract

Due to their DNA-intercalating agents 9-aniliinoacridines play an important role as antitumor agents. A Series of some Chalcone substituted 9-aniliinoacridines 1a-x were designed for their anti-breast cancer activity. Molecular docking studies were performed by Glide module of Schrodinger suite-2016, targeted against Human epidermal growth factor receptor HER2 (PDB id-3PP0). In-silico ADMET screening by qikprop module and binding free energy by Prime-MMGBSA module also performed. Based on the binding affinity of the designed molecules with HER2 on the basis of GLIDE score and interaction patterns. Most of the compounds 1a-x have significant Glide scores when compared with standard anticancer drugs ledacrine and tamoxifen. Most of the Chalcone substituted 9-anilinoacridine derivatives 1a-x have good binding affinity with Glide score in the range of -5. 32 to -9.37 compared with the standard ledacrine (-5.23) and tamoxifen (-3.78). The results reveals that, Chalcone substituted 9-amino acridines as HER2 inhibitor and the compounds, 1g, f, b, h, t, u with good Glide score may produce significant anti-breast cancer activity for further refinement.

Published in International Journal of Computational and Theoretical Chemistry (Volume 7, Issue 1)
DOI 10.11648/j.ijctc.20190701.12
Page(s) 6-13
Creative Commons

This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited.

Copyright

Copyright © The Author(s), 2019. Published by Science Publishing Group

Keywords

Docking Studies, Acridine, Chalcone, MM-GBSA, Antibreast Cancer, HER2

References
[1] Zahi Mitri; Tina Constantine; and Ruth O’Regan., The HER2 Receptor in Breast Cancer: Pathophysiology, Clinical Use, and New Advances in Therapy. Chemotherapy Research and Practice. 2012, doi: 10. 1155/2012/743193.
[2] Elda Tagliabue; Andrea Balsari; Manuela Campiglio; Serenella M. Pupa. HER2 as a target for breast cancer therapy, Expert Opin. Biol. Ther. 2010, 10 (5), 711-724.
[3] Kallioniemi, O. P., Kallioniemi, A., Kurisu, W., Thor, A., Chen, L. C., Smith, H. S., Waldman, F. M., Pinkel, D., Gray, J. W. ERBB2 amplification in breast cancer analysed by fluorescence in situ hybridization Proc. Natl. Acad. Sci. USA. 1992, 89 (12), 5321-535.
[4] Carolina Gutierrez, M. D., Rachel Schiff, Ph. D. HER 2: Biology, Detection, and Clinical Implications. Arch Pathol Lab Med. 2011, 135 (1), 55–62.
[5] Nadaraj, V.; Selvi, S. T.; Mohan, S. Microwave-induced synthesis and anti-microbial activities of 7, 10, 11, 12-tetrahydrobenzo [c]acridin-8 (9H)-one derivatives. Eur. J. Med. Chem. 2009, 44, 976-982.
[6] Dickens, B. F.; Weglicki, W. B.; Boehme, P. A.; Mak, I. T. Antioxidant and lysosomotropic properties of acridine-propranolol: protection against oxidative endothelial cell injury. J. Mol. Cell Cardiol. 2002, 34, 129-137.
[7] Rouvier, C. S.; Barret, J. M.; Farrell, C. M.; Sharples, D.; Hill, B. T.; Barbe, J. Synthesis of 9-acridinyl sulfur derivatives: sulfides, sulfoxides and sulfones. Comparison of their activity on tumour cells. Eur. J. Med. Chem. 2004, 39, 1029-1038.
[8] Rastogi, K.; Chang, J. Y.; Pan, W. Y.; Chen, C. H.; Chou, T. C.; Chen L. T.; et al., Antitumor AHMA linked to DNA minor groove binding agents: synthesis and biological evaluation. J. Med. Chem. 2002, 45, 4485-4493.
[9] Kalirajan, R.; Vivek kulshrestha; Sankar, S.; Jubie, S. Docking studies, synthesis, characterization of some novel oxazine substituted 9-anilinoacridine derivatives and evaluation for their anti oxidant and anticancer activities as topo isomerase II inhibitors. Eur. J. Med. Chem. 2012, 56, 217-224.
[10] Bacherikov, V. A.; Chou, T. C.; Dong, H. J.; Chen, C. H.; Lin, Y. W.; Tsai, T. J. Potent antitumor N-mustard derivatives of 9-anilinoacridine, synthesis and antitumor evaluation. Bioorg. Med. Chem. Lett. 2004, 14, 4719-4722.
[11] Kalirajan, R.; Muralidharan, V.; Jubie, S.; Gowramma, B.; Gomathy, S.; Sankar, S.; Elango, K. Synthesis of some novel pyrazole substituted 9-anilino acridine derivatives and evaluation for their antioxidant and cytotoxic activities. J. Heterocycl. chem. 2012, 49, 748-754.
[12] Gamage, S. A.; Tepsiri, N.; Wilairat, P.; Wojcik, S. J.; Figgitt, D. P.; Ralph, R. K. et al. Synthesis and invitro evaluation of 9-anilino-3, 6-diaminoacridines active against a multidrug-resistant strain of the malaria parasite plasmodium falciparum. J. Med. Chem. 1994, 37, 1486-1494.
[13] Anderson, M. O.; Sherrill. J.; Madrid, P. B.; Liou, A. P.; Weisman, J. L.; De Risib, J. L.; et al. Parallel synthesis of 9-aminoacridines and their evaluation against chloroquine-resistant Plasmodium falciparum. Bioorg. Med. Chem. 2006, 14, 334-43.
[14] Chen, Y. L.; Lu, C. M.; Chen, I. L.; Tsao, L. T.; Wang, J. P. Synthesis and antiinflammatory evaluation of 9-anilinoacridine and 9-phenoxyacridine derivatives. J. Med. Chem. 2002, 45 (21), 4689-4694.
[15] Sondhi, S. M.; Johar, M.; Nirupama, S.; Sukla, R.; Raghubir, R. S. G. Synthesis of sulpha drug acridine derivatives and their evaluation for anti-anflammatory, analgesic and anticancer acvity. Indian J. Chem. 2002, 41B, 2659-2666.
[16] Gamage, S. A.; Figgitt, D. P.; Wojcik, S. J.; Ralph, R. K.; Ransijn, A.; Mauel, J.; et al. Structure-activity relationships for the antileishmanial and antitrypanosomal activities of 1'-substituted 9-anilinoacridines. J. Med. Chem., 1997, 40, 2634-2642.
[17] Llama, E. F.; Campo, C. D.; Capo, M.; Anadon, M. Synthesis and antinociceptive activity of 9-phenyl-oxy or 9-acyl-oxy derivatives of xanthene, thioxanthene and acridine. Eur. J. Med. Chem. 1989, 24, 391-396.
[18] Recanatini, M.; Cavalli, A.; Belluti, F.; Piazzi, L.; Rampa, A.; Bisi, A.; et al. SAR of 9-amino-1, 2, 3, 4-tetrahydroacridine-based acetyl cholinesterase inhibitors: synthesis, enzyme inhibitory activity, QSAR, and structure-based CoMFA of tacrine analogues. J. Med. Chem. 2000, 43 (10), 2007-2018.
[19] Goodell, J. R.; Madhok, A. A.; Hiasa, H.; Ferguson, D. M. Synthesis and evaluation of acridine- and acridone-based anti-herpes agents with topoisomerase activity. Bioorg. Med. Chem. 2006, 14, 5467-5480.
[20] Harrison, R. J., Cuesta, J., Chessari, G., Read, M. A., Basra, S. K., Reszka, A. P. et al. Trisubstituted acridine derivatives as potent and selective telomerase inhibitors. J. Med. Chem. 2003, 46, 4463-4476.
[21] Guodong Shen, Dingben Chen, Yiliang Zhang, Manman Sun, Kai Chen, Cong Jin, Kaining Li, Weiliang Bao. Synthesis of benzoxazine and 1, 3-oxazine derivatives via ligand-free copper (I)-catalyzed one-pot cascade addition/cyclization reaction. Tetrahedron. 2012; 68, 166-72.
[22] Kalirajan, R.; Sivakumar, S. U.; Jubie, S.; Gowramma, B.; Suresh, B. Synthesis and biological evaluation of some heterocyclic derivatives of chalcones. Int. J. Chemtech. Res. 2009, 1, 27-34.
[23] Kalirajan, R.; Pandiselvi, M.; Sankar, S.; Gowramma, B. Molecular Docking Studies and Insilico ADMET Screening of Some Novel Chalcone Substituted 9-Anilinoacridines as Topoisomerase II Inhibitors, SF J. Pharm. Anal. Chem., 2018; 1 (1): 1004.
[24] Kalirajan, R., Mohammed rafick, M. H., Jubie, S., Sankar, S. Docking studies, synthesis, characterization and evaluation of their antioxidant and cytotoxic activities of some novel isoxazole substituted 9-anilinoacridine derivatives. The Sci. World J. 2012, doi: 10. 1100/2012/165258.
[25] Rajagopal Kalirajan; Muralidharan, V.; Selvaraj Jubie and Sankar. S. Microwave assisted Synthesis, Characterization and Evaluation for their Antimicrobial Activities of Some Novel pyrazole substituted 9-Anilino Acridine Derivatives. Int. J. Health and Allied Sci. 2013, 2 (2), 81-87.
[26] Kalirajan, R; Gowramma, B; Jubie, S and Sankar S. Molecular Docking Studies and In-silico ADMET Screening of Some Novel Heterocyclic Substituted 9-Anilinoacridines as Topoisomerase II Inhibitors. JSM Chem, 2017, 5 (1), 1039-1044.
[27] Kalirajan, R; Vivek kulshrestha; Jubie, S and Sankar S. Synthesis, Characterization and Evaluation for Antitumour Activity of Some Novel Oxazine Substituted 9-Anilinoacridines and their 3D-QSAR Studies. Indian J. Pharm. Sci. 2018, 80 (5), 921-929.
[28] Kalirajan, R; Sankar, S; Jubie, S and Gowramma, B. Molecular Docking studies and in-silico ADMET Screening of Some novel Oxazine substituted 9-Anilinoacridines as Topoisomerase II Inhibitors. Indian J. Pharm. Educ. Res., 2017, 51 (1), 110-115.
[29] Halperin, I.; Ma, B.; Wolfson, H.; Nussinov, R. Principles of Docking: An Overview of Search Algorithms and a Guide to Scoring Functions. PROTEINS: St Fun Gen. 2002, 47, 409-43.
[30] Naga Srinivas Tripuraneni, Mohammed. Afzal Azam, Pharmacophore modelling, 3D-QSAR and docking study of 2-phenylpyrimidine analogues as selective PDE4B inhibitors, J Theoretical Biology, 2016, 394, 117-126.
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    Kalirajan Rajagopal, Pandiselvi Arumugasamy, Gowramma Byran. (2019). In-silico Drug Design, ADMET Screening, MM-GBSA Binding Free Energy of Some Chalcone Substituted 9-Anilinoacridines as HER2 Inhibitors for Breast Cancer. International Journal of Computational and Theoretical Chemistry, 7(1), 6-13. https://doi.org/10.11648/j.ijctc.20190701.12

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    ACS Style

    Kalirajan Rajagopal; Pandiselvi Arumugasamy; Gowramma Byran. In-silico Drug Design, ADMET Screening, MM-GBSA Binding Free Energy of Some Chalcone Substituted 9-Anilinoacridines as HER2 Inhibitors for Breast Cancer. Int. J. Comput. Theor. Chem. 2019, 7(1), 6-13. doi: 10.11648/j.ijctc.20190701.12

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    AMA Style

    Kalirajan Rajagopal, Pandiselvi Arumugasamy, Gowramma Byran. In-silico Drug Design, ADMET Screening, MM-GBSA Binding Free Energy of Some Chalcone Substituted 9-Anilinoacridines as HER2 Inhibitors for Breast Cancer. Int J Comput Theor Chem. 2019;7(1):6-13. doi: 10.11648/j.ijctc.20190701.12

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  • @article{10.11648/j.ijctc.20190701.12,
      author = {Kalirajan Rajagopal and Pandiselvi Arumugasamy and Gowramma Byran},
      title = {In-silico Drug Design, ADMET Screening, MM-GBSA Binding Free Energy of Some Chalcone Substituted 9-Anilinoacridines as HER2 Inhibitors for Breast Cancer},
      journal = {International Journal of Computational and Theoretical Chemistry},
      volume = {7},
      number = {1},
      pages = {6-13},
      doi = {10.11648/j.ijctc.20190701.12},
      url = {https://doi.org/10.11648/j.ijctc.20190701.12},
      eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.ijctc.20190701.12},
      abstract = {Due to their DNA-intercalating agents 9-aniliinoacridines play an important role as antitumor agents. A Series of some Chalcone substituted 9-aniliinoacridines 1a-x were designed for their anti-breast cancer activity. Molecular docking studies were performed by Glide module of Schrodinger suite-2016, targeted against Human epidermal growth factor receptor HER2 (PDB id-3PP0). In-silico ADMET screening by qikprop module and binding free energy by Prime-MMGBSA module also performed. Based on the binding affinity of the designed molecules with HER2 on the basis of GLIDE score and interaction patterns. Most of the compounds 1a-x have significant Glide scores when compared with standard anticancer drugs ledacrine and tamoxifen. Most of the Chalcone substituted 9-anilinoacridine derivatives 1a-x have good binding affinity with Glide score in the range of -5. 32 to -9.37 compared with the standard ledacrine (-5.23) and tamoxifen (-3.78). The results reveals that, Chalcone substituted 9-amino acridines as HER2 inhibitor and the compounds, 1g, f, b, h, t, u with good Glide score may produce significant anti-breast cancer activity for further refinement.},
     year = {2019}
    }
    

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  • TY  - JOUR
    T1  - In-silico Drug Design, ADMET Screening, MM-GBSA Binding Free Energy of Some Chalcone Substituted 9-Anilinoacridines as HER2 Inhibitors for Breast Cancer
    AU  - Kalirajan Rajagopal
    AU  - Pandiselvi Arumugasamy
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    DO  - 10.11648/j.ijctc.20190701.12
    T2  - International Journal of Computational and Theoretical Chemistry
    JF  - International Journal of Computational and Theoretical Chemistry
    JO  - International Journal of Computational and Theoretical Chemistry
    SP  - 6
    EP  - 13
    PB  - Science Publishing Group
    SN  - 2376-7308
    UR  - https://doi.org/10.11648/j.ijctc.20190701.12
    AB  - Due to their DNA-intercalating agents 9-aniliinoacridines play an important role as antitumor agents. A Series of some Chalcone substituted 9-aniliinoacridines 1a-x were designed for their anti-breast cancer activity. Molecular docking studies were performed by Glide module of Schrodinger suite-2016, targeted against Human epidermal growth factor receptor HER2 (PDB id-3PP0). In-silico ADMET screening by qikprop module and binding free energy by Prime-MMGBSA module also performed. Based on the binding affinity of the designed molecules with HER2 on the basis of GLIDE score and interaction patterns. Most of the compounds 1a-x have significant Glide scores when compared with standard anticancer drugs ledacrine and tamoxifen. Most of the Chalcone substituted 9-anilinoacridine derivatives 1a-x have good binding affinity with Glide score in the range of -5. 32 to -9.37 compared with the standard ledacrine (-5.23) and tamoxifen (-3.78). The results reveals that, Chalcone substituted 9-amino acridines as HER2 inhibitor and the compounds, 1g, f, b, h, t, u with good Glide score may produce significant anti-breast cancer activity for further refinement.
    VL  - 7
    IS  - 1
    ER  - 

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Author Information
  • Department of Pharmaceutical Chemistry, JSS College of Pharmacy [A Constituent College of JSS Academy of Higher Education & Research-(Deemed to Be University)], Udhagamandalam, Tamilnadu, India

  • Department of Pharmaceutical Chemistry, JSS College of Pharmacy [A Constituent College of JSS Academy of Higher Education & Research-(Deemed to Be University)], Udhagamandalam, Tamilnadu, India

  • Department of Pharmaceutical Chemistry, JSS College of Pharmacy [A Constituent College of JSS Academy of Higher Education & Research-(Deemed to Be University)], Udhagamandalam, Tamilnadu, India

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