A physically interpretable quantum-theoretic QSAR for some carbonic anhydrase inhibitors with diverse aromatic rings, obtained by a new QSAR procedure.
A QSAR based almost entirely on quantum theoretically calculated descriptors has been developed for a large and heterogeneous group of aromatic and heteroaromatic carbonic anhydrase inhibitors, using orbital energies, nodal angles, atomic charges, and some other intuitively appealing descriptors. Most calculations have been done at the B3LYP/6-31G* level of theory. For the first time we have treated five-membered rings by the same means that we have used for benzene rings in the past. Our flip regression technique has been expanded to encompass automatic variable selection. The statistical quality of the results, while not equal to those we have had with benzene derivatives, is very good considering the noncongeneric nature of the compounds. The most significant correlation was with charge on the atoms of the sulfonamide group, followed by the nodal orientation and the solvation energy calculated by COSMO and the charge polarization of the molecule calculated as the mean absolute Mulliken charge over all atoms.
Clare
Brian W
BW
School of Biomedical and Chemical Science, The University of Western Australia, 35 Stirling Highway, Crawley WA 6009, Australia. bwc@theochem.uwa.edu.au
Supuran
Claudiu T
CT
D001391:Azo Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
D001391:Azo Compounds; D002257:Carbonic Anhydrase Inhibitors; D007527:Isoenzymes; D013449:Sulfonamides; D002256:Carbonic Anhydrases