Journal of Molecular Modeling

, Volume 18, Issue 7, pp 3389–3413

Pharmacophore, QSAR, and ADME based semisynthesis and in vitro evaluation of ursolic acid analogs for anticancer activity

  • Komal Kalani
  • Dharmendra Kumar Yadav
  • Feroz Khan
  • Santosh K. Srivastava
  • Nitasha Suri
Original Paper

DOI: 10.1007/s00894-011-1327-6

Cite this article as:
Kalani, K., Yadav, D.K., Khan, F. et al. J Mol Model (2012) 18: 3389. doi:10.1007/s00894-011-1327-6

Abstract

In the present work, QSAR models for predicting the activities of ursolic acid analogs against human lung (A-549) and CNS (SF-295) cancer cell lines were developed by a forward stepwise multiple linear regression method using a leave-one-out approach. The regression coefficient (r2) and the cross-validation regression coefficient (rCV2) of the QSAR model for cytotoxic activity against the human lung cancer cell line (A-549) were 0.85 and 0.80, respectively. The QSAR study indicated that the LUMO energy, ring count, and solvent-accessible surface area were strongly correlated with anticancer activity. Similarly, the QSAR model for cytotoxic activity against the human CNS cancer cell line (SF-295) also showed a high correlation (r2 = 0.99 and rCV2 = 0.96), and indicated that dipole vector and solvent-accessible surface area were strongly correlated with activity. Ursolic acid analogs that were predicted to be active against these cancer cell lines by the QSAR models were semisynthesized and characterized on the basis of their 1H and 13C NMR spectroscopic data, and were then tested in vitro against the human lung (A-549) and CNS (SF-295) cancer cell lines. The experimental results obtained agreed well with the predicted values.

Keywords

QSAR Ursolic acid analogs In vitro cytotoxic activity ADME 

Supplementary material

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Komal Kalani
    • 1
  • Dharmendra Kumar Yadav
    • 2
  • Feroz Khan
    • 2
  • Santosh K. Srivastava
    • 1
  • Nitasha Suri
    • 3
  1. 1.Analytical Chemistry DepartmentCentral Institute of Medicinal and Aromatic PlantsLucknowIndia
  2. 2.Metabolic & Structural Biology DepartmentCentral Institute of Medicinal and Aromatic PlantsLucknowIndia
  3. 3.Pharmacology DivisionIndian Institute of Integrative MedicineJammuIndia

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