Document Type
Article
Publication Date
2-2019
Abstract
A series of novel chromone/aza-chromone fused α-aminophosphonate derivatives were synthesized in good yields using silica chloride as the catalyst. All the synthesized compounds were tested for their c-Src kinase inhibitory activity. Aza-chromone compound showed Src kinase inhibition with an IC50 value of 15.8 µM. The compounds were subjected to molecular docking and dynamics simulations to study the atomic level interactions with an unphosphorylated proto-oncogenic tyrosine protein kinase Src (PDB code 1Y57) as well as phosphorylated tyrosine protein kinase Src (PDB code 2H8H). Docking and molecular dynamic results revealed phosphorylated Src tyrosine kinase protein better results than unphosphorylated tyrosine Src kinase protein. Chemoinformatics study revealed the compounds had lead like properties. Machine learning (SVR) models were built to study the structure activity correlations. A CC of 0.835 was obtained when the SVR model was applied to the 17 synthesized compounds. It is envisaged that the work will provide guidelines for future drug design efforts for Src kinase inhibitors.
Recommended Citation
Bapat S, Viswanadh N, Mujahid M, et al. Synthesis, biological evaluation and molecular modeling studies of novel chromone/aza-chromone fused alpha-aminophosphonates as Src kinase inhibitors. Journal of Scientific & Industrial Research. 2019;78(2):111-117.
Copyright
The authors
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.5 License.
Included in
Amino Acids, Peptides, and Proteins Commons, Medical Biochemistry Commons, Medicinal-Pharmaceutical Chemistry Commons, Other Pharmacy and Pharmaceutical Sciences Commons, Pharmaceutics and Drug Design Commons
Comments
This article was originally published in Journal of Scientific and Industrial Research, volume 78, issue 2, in 2019.