QSAR studies for the inhibition of the transmembrane carbonic anhydrase isozyme XIV with sulfonamides using PRECLAV software

Abstract

QSAR studies for the inhibition of isozyme XIV of human carbonic anhydrase (CA, EC 4.2.1.1) by a series of sulfonamides including clinically used derivatives (acetazolamide, methazolamide, ethoxzolamide, dichlorophenamide, dorzolamide, brinzolamide, benzolamide, and zonisamide) are presented. Statistical calculations done using the PRECLAV program, for the correlation between the observed inhibition values and the calculated ones were good (s ¼ 0.2416, r 2 ¼ 0.9259, F ¼ 75.0196, r 2 CV ¼ 0:8985). The obtained results by using PRECLAV descriptors have been compared with those where the descriptors have been calculated with HYPERCHEM. The obtained QSAR equations pointed out the fact that the CA inhibitory activity decreased for unsubstituted (at the organic scaffold) aromatic/heteroaromatic sulfonamides, but was favored by the presence of alkyl groups substituting the scaffold, which led to a higher internal topological diversity, as well as by the presence of condensed aromatic rings in the structure of these enzyme inhibitors.

3D-QSAR CoMFA studies on sulfonamide inhibitors of the Rv3588c β-carbonic anhydrase from Mycobacterium tuberculosis and design of not yet synthesized new molecules

“…QSAR finds the parameters of the compounds that govern their biological activities and throw the light on their mechanism of action. Both these aspects of QSAR greatly help modify the structures of the compounds leading to compounds of high therapeutic value [19][20][21][22][23][24][25] .…”

QSAR analysis of Mur B inhibitors with antibacterial properties discussing role of physico-chemical parameters

“…In an attempt to determine the role of structural features, which appear to influence the observed activity of reported compounds, QSAR studies were undertaken using linear free energy relationship (LFER) model proposed by Hansch and Fujita (Srivastava et al, 2009a, b). A large number of such indices are available in the literature, which are widely used in drug modeling and also in establishing QSARs (Srivastava et al, 2008a, b, c;Agarwal et al, 2003Agarwal et al, , 2005Agarwal et al, , 2006Khadikar et al, 2002Khadikar et al, , 2003aKhadikar et al, , b, 2005aSingh et al, 2009).…”

Modeling of novel HIV-1 protease inhibitors incorporating N-Aryl-oxazolidinone-5-carboxamides as P2 ligands using quantum chemical and topological finger print descriptors

“…Separately, for each molecule, more than the 200 topological fingerprint descriptors (binary and frequency finger print) specific to the DRAGON 5.5 program have been calculated (Talete srl, 2007). The statistical calculations used for obtaining the QSAR equations were done again with PRECLAV, as reported earlier (Tarko, 2007;Tarko and Supuran Claudiu, 2007;Singh et al, 2009;Singh, 2009).…”