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.canis increased with increase in the experimental and theoretical log P values, but this increase was only significant for the activity against Microsporum. canis.