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Inverse QSAR approach and Molecular docking studies to design novel methoxy substituted Chalcones and their Computational Anticancer activity evaluation

Author Affiliations

  • 1Dept. of Chemistry, Govt. Nirbhay Singh Patel Science College, Indore, MP, INDIA
  • 2Dept. of Chemistry, Govt. Holkar Science College, Indore, MP, INDIA
  • 3Dept. of Pharmaceutical Chemistry, Softvision College, Indore, MP, INDIA

Res.J.chem.sci., Volume 4, Issue (3), Pages 76-80, March,18 (2014)


Quantitative structure activity-relationship (QSAR) studies have emerged as promising tool to in silico prediction and optimization of potential bioactive compounds. The purpose of QSAR studies is to save time, cost, and animal toxicity and to support green chemistry. Present studies are efforts to design and identify novel chalcones having high potency and selectivity. Present investigations identify structural insights of methoxy substituted chalcones in Linear and non-linear QSAR models. QSAR studies identify the profound non-linear relationship among structures of methoxy substituted chalcones and their biological activity measures (IC50). It concludes that any structural variation in present class of chalcones would bring a non-linear change in IC50. MLR produced efficient QSAR models (R2 = 0.809). We have designed new candidates employing structure-activity relationship obtained from QSAR models. Descriptor based inverse QSAR approach has been applied in computational modeling of new small molecules. Furthermore, they have been compared with synthesized dataset of methoxy substituted chalcones using molecular docking and ADMET studies. In course of molecular docking studies, newly designed molecules yielded promising results with better binding capacity (Docking rerank Score -103.089) than previously synthesized compounds. Computational pharmacokinetic and pharmacodynamic (ADMET) studies revealed their better intestinal absorption, skin permeability and blood brain barrier penetration. The aim of our work is computational designing of novel methoxy substituted chalcones using QSAR and flexible molecular docking based techniques.


  1. Milne G.W.A., Pharmacophore and drug discovery, In Encyclopedia of computational chemistry; von Rague Schleyer, P., Ed.; Wiley: New York, USA, (1998)
  2. Dror O., Shulman-Peleg A., Nussinov R. and Wolfson H.J., Predicting molecular interactions insilico, February 6, (2004)
  3. Li X. and Lin J., QSAR modeling, J. Math. Chem., 33, 8189 (2003)
  4. Vogel S., Barbic M., Juergenliemk G. and Heilmann J., Synthesis, cytotoxicity, anti-oxidative and anti-inflammatory activity of chalcones and influence of A-ring modifications on the pharmacological effect, Eur. J. Med. Chem., 45(6), 2206-2213 (2010)
  5. Lv P.C., Li D.D., Li Q.S., Lu X., Xiao Z.P. and Zhu H.L., Synthesis, molecular docking and evaluation of thiazolyl-pyrazoline derivatives as EGFR TK inhibitors and potential anticancer agents, Bioorg. Med. Chem. Lett., 21(18), 5374-5377 (2012)
  6. Mourad M.A.E., Abdel A.M, Abuo R.G.D. and Farag H.H., Design, synthesis and anticancer activity of nitric oxide donating/chalcone hybrids, Eur. J. Med. Chem., 54, 907-913 (2012)
  7. Mullen L.M.A., Duchowicz P.R. and Castro E.A., QSAR treatment on a new class of triphenylmethyl-containing compounds as potent anticancer agents, Chemometr. Intell. Lab., 107(2), 269-275 (2012)
  8. Sivakumar P.M., Iyer G., Natesan L. and Doble M., 3'-Hydroxy-4-methoxychalcone as a potential antibacterial coating on polymeric biomaterials, Appl . Surf. Sci., 256(20), 6018-6024 (2010)
  9. Bandgar B.P. and Gawande S.S., Synthesis and biological screening of a combinatorial library of [beta]-chlorovinyl chalcones as anticancer, anti-inflammatory and antimicrobial agents, Bioorg. Med. Chem., 18(5), 2060-2065 (2010)
  10. Lai C.H., Rao Y.K., Fang, S.H, Sing Y.T. and Tzeng Y.M., Identification of 3', 4', 5'-trimethoxychalcone analogues as potent inhibitors of Helicobacter pylori-induced inflammation in human gastric epithelial cells, Bioorg. Med. Chem. Lett., 15; 20(18), 5462-5465 (2010)
  11. Yang E.B., Guo Y.J., Zhang K., Chen Y.Z. and Mack P., Inhibition of epidermal growth factor receptor tyrosine kinase by chalcone derivatives, Biochim. Biophys. Acta., 1550(2), 144-152 (2001)
  12. Khatib S., Nerya O., Musa R., Shmuela M., Tamira S. and Vaya J., Chalcones as potent tyrosinase inhibitors: the importance of a 2, 4-substituted resorcinol moiety,Bioorg Med Chem., 13(2), 433-441 (2005)
  13. Lawrence N.J., Mc. Gown A. T., Ducki S. and Hadfield J.A., The interaction of chalcones with tubulin, Anti. Canc. Drug. Des., 15(2), 135-141 (2000)
  14. Zhang H., Liu J.J., Sun J., Yang X.H., Zhao T.T., Lu X., Gong H.B. and Zhu H.L., Design, synthesis and biological evaluation of novel chalcone derivatives as antitubulin agents, Bioorg. Med. Chem., 15;20(10), 3212-3218 (2012)
  15. Mojzis J., Varinska L., Mojzisova G., Kostova I. and Mirossay L., Antiangiogenic effects of flavonoids and chalcones, Pharmacol. Res., 57(4), 259-265 (2008)
  16. Pilatova M., Varinska L., Perjesi P., Sarissky M., Mirossay L., Solar P., Ostro A. and Mojzis J., In vitro antiproliferative and antiangiogenic effects of synthetic chalcone analogues, Toxicol. in vitro, 24(5), 1347-1355 (2010)
  17. Hijova E., Bioavailability of chalcones, Bratisl. Lek. Listy., 107(3), 80 (2006)
  18. Kalani K., Yadav D. K., Khan F., Srivastava S.K., Suri N., Pharmacophore, QSAR, and ADME based semisynthesis and in vitro evaluation of ursolic acid analogs for anticancer activity, J. Mol. Model., 18(7), 1-25 (2012)
  19. Liu T., Tang G.W. and Capriotti E., Comparative modeling: the state of the art and protein drug target structure prediction. Comb. Chem. High Throughput Screen, 14(6), 532-47 (2011)
  20. Yang J.M. and Chen, C.C., GEMDOCK: A generic evolutionary method for molecular docking, Proteins, 55(2), 288-304 (2004)
  21. Gehlhaar D.K., Verkhivker G., Rejto P.A., Fogel D.B., Fogel L.J. and Freer S.T., Docking conformationally flexible small molecules into a protein binding site through evolutionary programming, Proceedings of the Fourth International Conference on Evolutionary Programming, San Diego, Cambridge, 615-27 (1995)
  22. Gehlhaar D.K., Bouzida D. and Rejto P.A., Fully automated and rapid flexible docking of inhibitors covalently bound to serine proteases. Proceedings of the Seventh International Conference on Evolutionary Programming, San Diego, Cambridge, 449-461 (1996)
  23. Pandey, N., Yadav, M, Nayarisseri, A., Ojha, M., Prajapati, J. Cross evaluation of different classes of alpha-adrenergic receptor antagonists to identify overlapping pharmacophoric requirements, J. Pharm. Research,6(1), 173-178 (2013)
  24. Bachwani M., Kumar R., Molecular Docking: A review,IJRAP, 2(6), 1746-1751 (2011)