2D-QSAR and HQSAR of the inhibition of calcineurin-NFAT signaling by blocking protein-protein interaction with N-(4-oxo-1 (4H)-naphthalenylidene)benzenesulfonamide analogues

Abstract

The inhibition of calcineurin-NFAT signaling by blocking protein-protein interaction with N-(4-oxo-1(4H)-naphthalenylidene)benzenesulfonamide analogues was studied in order to obtain mechanistic information about the effects of structural modification and molecular design of immunomodulation agents. The study was carried out by quantitative structure-activity relationship (QSAR) analysis using 2D-QSAR and hologram QSAR (HQSAR) methods. The statistical results of the two models showed the best prediction and fitness (r2 > 0.900) for the inhibition activities. The inhibitory activities from the 2D-QSAR models were dependent upon the electronic affinity of electron acceptor and optimum dipole moment (DM opt = 4.491 Debye). In addition, the HQSAR model provided information about which structural distinctions could be significant contributors the inhibition.