Multiple Regression Analysis of Antimalarial Activities of Sulfones and Sulfonamides in Cell‐Free Systems and Principal Component Analysis to Compare with Antibacterial Activities

Abstract
The inhibition of dihydropteroate synthase extracts by sulfones and sulfonamides has been determined. Structural dependency of the observed I50‐values has been quantitatively explained by multiple regression and principal component analysis. New highly active sulfones have been synthesized guided by the derived QSAR. The analysis leads to the conclusion that electronic and steric substituent effects are decisive and that sulfones and sulfonamides are binding to the same receptor site. The LFE‐descriptors used are correlated with the minimal conformational entropy. The results are also compared with the results obtained in cell‐free and whole cell systems of bacteria. The additional influence of cell‐wall permeability on inhibitory efficacy is demonstrated.

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