Insights through AM1 calculations into the structural requirement of 3,4,6-substituted-2-quinolone analogs towards FMS kinase inhibitory activity.
In the present work, we focused on quantification of activity of 3,4,6-substituted-2-quinolone derivatives with reference to structural properties. The multi-variant regression expressions were developed through sequential multiple linear regression technique, considering adjustable correlation coefficient (r(adj)(2)). The amalgamated best fit consensus scoring function showed coefficient of determination (0.891), leave one out cross validated squared correlation coefficient (0.776) and external predictivity value (0.668). The detailed structural investigation revealed that the FMS kinase inhibitory activity is predominantly explained by the topological descriptor, functional group, RDF and MoRSE code. The structural insights gleaned from the study could be usefully employed to design inhibitors with a much more enhanced potency.
Department of Pharmaceutical Chemistry, Smriti College of Pharmaceutical Education, 4/1 Pipliya Kumar Kakad, Maya Kheri Road, Indore-452010, Madhya Pradesh, India. arunkg_73@hotmail.com
Arun Kumar
AK
Gupta
Neetu
N
Sabarwal
Yogesh P
YP
Agrawal
Sumeet
S
Prachand
Sanjay
S
Jain
D055598:Chemical Phenomena; D015195:Drug Design; D020128:Inhibitory Concentration 50; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D015363:Quinolones / Q000737:chemistry* / Q000494:pharmacology*; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000037:antagonists & inhibitors*; D012044:Regression Analysis
D047428:Protein Kinase Inhibitors; D015363:Quinolones; D016186:Receptor, Macrophage Colony-Stimulating Factor