Three-dimensional quantitative structure-activity relationship studies on c-Src inhibitors based on different docking methods.
c-Src kinase play an important role in cell growth and differentiation and its inhibitors can be useful for the treatment of various diseases, including cancer, osteoporosis, and metastatic bone disease. Three dimensional quantitative structure-activity relationship (3D-QSAR) studies were carried out on quinazolin derivatives inhibiting c-Src kinase. Molecular field analysis (MFA) models with four different alignment techniques, namely, GLIDE, GOLD, LIGANDFIT and Least squares based methods were developed. glide based MFA model showed better results (Leave one out cross validation correlation coefficient r(2)(cv) = 0.923 and non-cross validation correlation coefficient r(2)= 0.958) when compared with other models. These results help us to understand the nature of descriptors required for activity of these compounds and thereby provide guidelines to design novel and potent c-Src kinase inhibitors.
Bairy
Santhosh Kumar
SK
bioCampus, GVK Biosciences, S-1, Phase-1, Technocrats Industrial Estate, Balanagar, Hyderabad 500 037, AP, India.
Suneel Kumar
B V S
BV
Bhalla
Joseph Uday Tej
JU
Pramod
A B
AB
Ravikumar
Muttineni
M
D000081247:CSK Tyrosine-Protein Kinase; D020134:Catalytic Domain; D003198:Computer Simulation; D018360:Crystallography, X-Ray; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D008968:Molecular Conformation; D011485:Protein Binding; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D021281:Quantitative Structure-Activity Relationship; D011799:Quinazolines / Q000737:chemistry* / Q000378:metabolism*; D019061:src-Family Kinases
D008024:Ligands; D011799:Quinazolines; D011505:Protein-Tyrosine Kinases; D000081247:CSK Tyrosine-Protein Kinase; D019061:src-Family Kinases; C000631346:CSK protein, human