QSAR AND MOLECULAR MODELING FOR A SERIES OF ISOMERIC X-SULFANILAMIDO-1-PHENYLPYRAZOLES

The influence of large substituents in o-, m- and p-positions of the p henyl ring of isomeric 3-, 4- and 5-sulfanilamido-1-phenylpyrazoles on their inhibitory effect against E.coli derived dihydropteroic acid sy nthase and whole cell E.coli has been studied. According to their pKa values, the 3- and 5-series show high antibacterial activity while the 4-series displays feeble inhibitory activity. In the 3-series the var iation in MIC is explained by differences in pKa (Hammett sigma) and m olecular weight (MW) or substituent surface respectively, whereas in t he 5-series steric effects of substituents in the o-position of the 1- phenyl ring and MW describe the differences in whole cell activity. In the cell-free system the inhibitory activity depends for the 3-series solely on pKa or Hammett sigma, respectively, and in the 5-series, wh ere the derivatives are almost completely ionized, the variation is so lely explainable by the steric effect of the substituents in o-positio n. The steric effect of o-substituents in the 5-series has been studie d and explained by NMR- and molecular modelling techniques. The observ ed differences in electronic effects of substituents comparing the 3- and 4-series with the 5-series could be explained by the results of qu antum chemical calculations.