English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Computational Docking Studies of Novel Heterocyclic Carboxamides as Potential PI3Kα Inhibitors

MPS-Authors
/persons/resource/persons84245

Sweidan,  K
Department High-Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Max Planck Society;

/persons/resource/persons83903

Engelmann,  J
Department High-Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Max Planck Society;

Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Sweidan, K., Sabbah, D., Engelmann, J., Abdel-Halim, H., & Abu Sheikha, G. (2015). Computational Docking Studies of Novel Heterocyclic Carboxamides as Potential PI3Kα Inhibitors. Letters in Drug Design Discovery, 12(10), 856-863. doi:10.2174/1570180812666150529205248.


Cite as: http://hdl.handle.net/11858/00-001M-0000-002A-437C-F
Abstract
Drugs comprising a heterocyclic system show widespread therapeutic impact such as antimicrobial, antidepressant, antihypertensive, and anticancer activity. We describe herein computational studies that support the promising biological activity of four new compounds (5, 6, 10 and 13). The wild-type and mutant phosphatidylinositol-4,5-bisphosphate 3-kinaseα (PI3Kα) proteins were used as models to explore the potential interaction of the designed molecules with this important kinase involved in the growth regulation of cancer cells. The results of our studies showed that the verified compounds ought to fit into the kinase domain of wild-type and mutant PI3Kαs. It is predicted that they interact with S774, K802, Y836, V851, S854, T856, Q859, and D933 that are known to be key binding residues for active inhibitors both in wild-type and mutant PI3Kαs. Docking scores infer the selectivity of compounds 5, 6 and 10 toward the mutant PI3Kα (H1047R), whereas compound 13 displayed a slightly higher affinity to the wild-type protein. The pharmacophore modeling of PI3Kα inhibitors showed that the explored compounds shared four out of five pharmacophoric points with such inhibitors. Thus, the recently developed four compounds might be recruited as lead structures for the design of new antitumor drugs targeting PI3Kα.