A DFT Study of the Relationships between the Electronic Structures of a series of 2,4,5- Trisubstituted Pyrimidines and their Inhibition of four Cyclin-dependent Kinases and their Anti-Proliferative Action against HCT-116 and MCF-7 Cell Lines.

Javier Valdebenito-Gamboa; Juan S. GÃƒÆ’Ã‚Â³mez-Jeria

Abstract

A DFT Study of the Relationships between the Electronic Structures of a series of 2,4,5- Trisubstituted Pyrimidines and their Inhibition of four Cyclin-dependent Kinases and their Anti-Proliferative Action against HCT-116 and MCF-7 Cell Lines.

Author(s): Javier Valdebenito-Gamboa, Juan S. GÃÆÃâÃâÃÂ³mez-Jeria

We present a study of the relationships between the electronic structures of a series of 2,4,5-trisubstituted pyrimidines and their inhibition of four cyclin-dependent kinases. Also we present a similar analysis concerning their anti-proliferative action against the MCF-7 and HCT-116 cell lines. The electronic structure of all the molecules was obtained using Density Functional Theory at the B3LYP/6-31g(d,p) level with full geometry optimization. We found statistically significant relationships between the variation of several local atomic reactivity indices and the variation of biological activity for all cases analyzed. The corresponding partial pharmacophores are proposed. In the case of the anti-proliferative action against MCF-7 and HCT-116 cell lines, the results strongly suggest that the site of action of all the molecules studied is located somewhere in the cell replication system. The possible relationships between the molecular electrostatic potential structure and the partial pharmacophores are discussed for some examples.

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