Three-Dimensional Pharmacophore Mapping of Certain Anticancer α-Methylene-γ-Butyrolactones
Abstract:A definition of pharmacophore hypotheses for certain anticancer α-methylene-γ-butyrolactones was carried out by consideration of a three-dimensional model that correlates the chemical structures of a series of α-methylene-γ-butyrolactones with their cytostatic activity. Training sets consisting of 20 α-methylene-γ-butyrolactones were selected in each case on the basis of the information content of the structures and the activity data as required by the HypoGen program in the Catalyst software. In this case, the best pharmacophore in terms of statistics and predictive value consisted of four features: two hydrogen bond acceptors (HBA), one hydrophobic (HP) feature, and one aromatic ring (AR) feature. The selected pharmacophore hypothesis yielded a correlation coefficient of 0.942 with a cost difference (null cost minus total cost) of 40.342. The pharmacophore was validated on a set of test compounds. This validation study provided confidence for the usefulness of the selected pharmacophore model to identify compounds with diverse structures from a database search. This investigation has demonstrated a practical approach toward the development of anticancer lead compounds through a three-dimensional pharmacophore mapping.
Document Type: Research Article
Publication date: 2003-01-01
More about this publication?
- Formerly: Oncology Research Incorporating Anti-Cancer Drug Design
Oncology Research Featuring Preclinical and Clincal Cancer Therapeutics publishes research of the highest quality that contributes to an understanding of cancer in areas of molecular biology, cell biology, biochemistry, biophysics, genetics, biology, endocrinology, and immunology, as well as studies on the mechanism of action of carcinogens and therapeutic agents, reports dealing with cancer prevention and epidemiology, and clinical trials delineating effective new therapeutic regimens.