Generic placeholder image

Medicinal Chemistry


ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

Computational Approaches to Improve Aggrecanase-1 Inhibitory Activity of (4-keto) Phenoxy) Methyl Biphenyl-4-sulfonamide: Group Based QSAR and Docking Studies

Author(s): Ponnurengam Malliappan Sivakumar, Naga Vignesh Selvaraj, G. Ramesh, J. Mohanapriya, Veluchamy Prabhawathi and Mukesh Doble

Volume 8 , Issue 4 , 2012

Page: [673 - 682] Pages: 10

DOI: 10.2174/157340612801216247

Price: $65


Group based Quantitative Structure Activity Relationship (GQSAR) was developed for thirty (4-keto-phenoxy) methyl biphenyl-4-sulfonamides which exhibit aggrecanase-1 enzyme inhibitory activity. This enzyme is involved in osteoarthritis. The data is divided into training and test sets, where the latter is used for validating the model. Substitution in the R1 position plays a major role when compared to substitution in R2 position. The former position is influenced by two descriptors, namely electrotopological and connectivity indices. R2 position is influenced by radius of gyration. The statistical parameters for the training set (r2 = 0.80, r2adj = 0.77, q2 = 0.69, F-ratio = 26.80 and standard error = 0.24) and the predicted r2 (r2 test =0.95) are satisfactory. Docking of the compounds with aggrecanase-1 enzyme showed that there is a strong negative correlation between the binding energy and aggrecanase -1 inhibitory activity. Compounds with the carbonyl substitution interact with the S'1 pocket which is needed for enhanced activity. The two methodologies described here can help in lead optimization.

Keywords: Aggrecanase, binding energy, docking, electrotopological descriptor, GQSAR, radius of gyration, biphenyl-4-sulfonamides, osteoarthritis, gyration, aggrecanase-1 enzyme

Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy