Computational Medicinal Chemistry to Design Novel Phosphoinositide 3- Kinase (PI3K) Alpha Inhibitors in View of Cancer

Title:Computational Medicinal Chemistry to Design Novel Phosphoinositide 3- Kinase (PI3K) Alpha Inhibitors in View of Cancer

Volume: 10 Issue: 3

Author(s): Lorane I. Hage-Melim, Cleydson B.R. Santos, Joao G. Poiani, Miguel de Menezes Vaidergom, Eduardo S. Manzolli and Carlos H.T. de Paula da Silva

Affiliation:

Keywords: Cancer therapy, medicinal chemistry, phosphoinositide 3-kinase (PI3K) inhibitors.

Abstract: Phosphoinositide 3-kinase (PI3K) is an enzyme involved in the signaling and control of essential cell functions with respect to receptor tyrosine kinase (RTK), for which they are activated. PI3K is involved in some types of cancers in humans, as has been observed in breast, hepatocellular, and colorectal, where, in this latter one, it was only the gene whose mutation was showed. When this gene mutation occurs, overstimulation of this pathway may occur, resulting in an overexpression of tyrosine kinase pathway and inactivation of the Phosphatase and tensin homolog (PTEN), which is a tumor suppressor most frequently deregulated in cancer. The present study aimed to investigate the known inhibitors of PI3K-alpha, deposited in databases such as Binding DB and PDB, in order to draw a profile of physicochemical and pharmacokinetic properties of the most active inhibitors for this enzyme. From this, nine proposals of potential new PI3K inhibitors were developed, which were evaluated with respect to pharmacokinetic and physicochemical properties, activity and toxicity predictions, as well as synthetic accessibility. The results suggest that some of the proposals may be promising new PIK3 inhibitors, containing drug properties.

Cite this article as:

Hage-Melim I. Lorane, Santos B.R. Cleydson, Poiani G. Joao, Vaidergom de Menezes Miguel, Manzolli S. Eduardo and Silva H.T. de Paula da Carlos, Computational Medicinal Chemistry to Design Novel Phosphoinositide 3- Kinase (PI3K) Alpha Inhibitors in View of Cancer, Current Bioactive Compounds 2014; 10 (3) . https://dx.doi.org/10.2174/157340721003141013142410