TY - JOUR
T1 - Anthranilate derivatives as TACE inhibitors
T2 - Docking based CoMFA and CoMSIA analyses
AU - Bahia, Malkeet Singh
AU - Gunda, Shravan Kumar
AU - Gade, Shwetha Reddy
AU - Mahmood, Saikh
AU - Muttineni, Ravikumar
AU - Silakari, Om
PY - 2011/1
Y1 - 2011/1
N2 - Anthranilic acid based derivatives (ANTs) have been identified as a novel class of potent tumor necrosis factor-α converting enzyme (TACE) inhibitors. A computational strategy based on molecular docking studies, followed by CoMFA and CoMSIA analyses has been performed to elucidate the atomic details of the TACE/ANT interactions and also to identify the most important features impacting TACE inhibitory activity of ANTs. The CoMSIA model resulted to be slightly more predictive than CoMFA model, and gave conventional r 2 0.991, r cv 2 0.793, q 2 0.777, SEE 0.050, F-value 655.610, and r test 2 0.871. The 3D-QSAR field contributions and the structural features of the TACE binding site showed a good correlation. These studies will be useful to design new TACE inhibitors with improved potency.
AB - Anthranilic acid based derivatives (ANTs) have been identified as a novel class of potent tumor necrosis factor-α converting enzyme (TACE) inhibitors. A computational strategy based on molecular docking studies, followed by CoMFA and CoMSIA analyses has been performed to elucidate the atomic details of the TACE/ANT interactions and also to identify the most important features impacting TACE inhibitory activity of ANTs. The CoMSIA model resulted to be slightly more predictive than CoMFA model, and gave conventional r 2 0.991, r cv 2 0.793, q 2 0.777, SEE 0.050, F-value 655.610, and r test 2 0.871. The 3D-QSAR field contributions and the structural features of the TACE binding site showed a good correlation. These studies will be useful to design new TACE inhibitors with improved potency.
KW - 3D-QSAR
KW - CoMFA
KW - CoMSIA
KW - Docking
KW - Rheumatoid arthritis
KW - TACE inhibitors
UR - http://www.scopus.com/inward/record.url?scp=78651459709&partnerID=8YFLogxK
U2 - 10.1007/s00894-010-0695-7
DO - 10.1007/s00894-010-0695-7
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C2 - 20349256
AN - SCOPUS:78651459709
SN - 1610-2940
VL - 17
SP - 9
EP - 19
JO - Journal of Molecular Modeling
JF - Journal of Molecular Modeling
IS - 1
ER -