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.
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.
Myung
Pyung-Keun
PK
Department of Pharmacy, College of Pharmacy, Chungnam National University, Daejeon, Korea.
Sung
Nack-Do
ND
D065095:Calcineurin Inhibitors; D007155:Immunologic Factors / Q000737:chemistry / Q000494:pharmacology; D008956:Models, Chemical; D015394:Molecular Structure; D050778:NFATC Transcription Factors / Q000037:antagonists & inhibitors*; D009281:Naphthalenes / Q000737:chemistry / Q000494:pharmacology; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D015398:Signal Transduction / Q000187:drug effects*; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology; D000096926:Benzenesulfonamides
D065095:Calcineurin Inhibitors; D007155:Immunologic Factors; D050778:NFATC Transcription Factors; D009281:Naphthalenes; D013449:Sulfonamides; C523772:N-(4-oxo-1(4H)-naphthalenylidene)benzenesulfonamide; D000096926:Benzenesulfonamides