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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)

Abstract

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.

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