02862nas a2200229 4500008004100000245015400041210006900195260000800264300001200272490000700284520205300291100001402344700001802358700001602376700002002392700001902412700001502431700002002446700002202466700001502488856012902503 2019 eng d00aSynthesis, biological evaluation and molecular modeling studies of novel chromone/Aza-Chromone fused alpha-aminophosphonates as src kinase inhibitors0 aSynthesis biological evaluation and molecular modeling studies o cFEB a111-1170 v783 a

A series of novel chromone/aza-chromone fused alpha-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 mu M. 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.

1 aBapat, S.1 aViswanadh, N.1 aMujahid, M.1 aShirazi, A., N.1 aTiwari, R., K.1 aParang, K.1 aKarthikeyan, M.1 aMuthukrishnan, M.1 aVyas, Renu uhttps://library.ncl.res.in/content/synthesis-biological-evaluation-and-molecular-modeling-studies-novel-chromoneaza-chromone01951nas a2200229 4500008004100000245015100041210006900192260000800261300001200269490000700281520111000288100001801398700001801416700001601434700002901450700001901479700002201498700003301520700002201553700001501575856013101590 2019 eng d00aSynthesis, biological evaluation and molecular modeling studies of novel chromone/Aza-chromone fused α-aminophosphonates as Src kinase inhibitors0 aSynthesis biological evaluation and molecular modeling studies o cFEB a111-1170 v783 aA 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.1 aBapat, Sanket1 aViswanadh, N.1 aMujahid, M.1 aShirazi, Amir, Nasrolahi1 aTiwari, Rakesh1 aParang, Keykavous1 aKarthikeyan, Muthukumarasamy1 aMuthukrishnan, M.1 aVyas, Renu uhttps://library.ncl.res.in/content/synthesis-biological-evaluation-and-molecular-modeling-studies-novel-chromoneaza-chromone-0