Correlation between lipophilicity and antimicrobial activity of some 2-(4-substituted phenyl)-3(2H)-isothiazolones

Background and purpose of the study . 3( 2H )-Isothiazolones have shown antimicrobial activity and have been used as preservative in different products. However, reports on their structure-antimicrobial activity relationship are scanty. The aim of this study was to determine the relationship between lipophilicity and antimicrobial activity of several 2- (4-substituted phenyl) -3( 2H )-isothiazolones of which some have shown antibacterial activities similar or higher than gentamycin, ceftazidime, ceftriaxone, ciprofloxacin , and antifungal activites similar or higher than itraconazole and ketoconazole as reference drugs. Methods. Partition coefficient (log P o/w ) of the tested compounds was determined experimentally by a reversed- phase high performance liquid chromatography method using octadecyl-poly(vinyl alcohol) (ODP) column and methanol-water gradient as mobile phase and theoretically by Clog P and ALOGPS computer programs. Results. The HPLC and theoretical log P o/w values showed potential correlations which indicate that both experimental and theoretical methods are equally suitable to predict lipophilicity of 3( 2H )-isothiazolones. There were also significant correlations between MICs (minimum inhibitory concentrations) of 5-chloro substituted 3( 2H )- isothiazolnes against Salmonella typhimurium and Escherichia coli and experimentally determined log P o/w values, as well as MICs of 5-unsubstituted 3( 2H )- isothiazolnes against E. coli and ALOGPS values. The antifungal activity of the tested compounds against Tricophyton. mentagrophytes and M. c anis increased with increase in the experimental and theoretical log P values , but this increase was only significant for the activity against Microsporum. canis.