Please use this identifier to cite or link to this item: http://nopr.niscair.res.in/handle/123456789/45761
Title: Synthesis, Biological Evaluation and Molecular Modeling Studies of Novel Chromone/Aza-Chromone Fused α-Aminophosphonates as Src Kinase Inhibitors
Authors: Bapat, S
Viswanadh, N
Mujahid, M
Shirazi, A N
Tiwari, R K
Parang, K
Karthikeyan, M
Muthukrishnan, M
Vyas, Renu
Keywords: Phosphorylated cSrc kinase;Cromone Compounds;Correlations;Tyrosine Kinase Protein;Proto-Oncogenic
Issue Date: Feb-2019
Publisher: NISCAIR-CSIR, India
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.
Page(s): 111-117
URI: http://nopr.niscair.res.in/handle/123456789/45761
ISSN: 0975-1084 (Online); 0022-4456 (Print)
Appears in Collections:JSIR Vol.78(02) [February 2019]

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