BIOLOGICAL STUDIES ON 1,2-BENZISOTHIAZOLE DERIVATIVES .5. ANTIMICROBIAL PROPERTIES OF N-ALKANOIC, N-ARYLALKANOIC AND N-ARYLOXYALKANOIC DERIVATIVES OF 1,2-BENZISOTHIAZOLIN-3-ONE - QSAR STUDY AND GENOTOXICITY EVALUATION

N-alkanoic, N-arylalkanoic and N-aryloxyalkanoic acids of 1,2-benzisot hiazolin-3-one, esters and amides of N-arylalkanoic and N-aryloxyalkan oic acids and 1,1-dioxides of N-arylalkanoic acids and esters were inv estigated for in vitro antimicrobial activity. N-arylalkanoic and N-ar yloxyalkanoic acids (compounds 4-12) and their esters and amides (comp ounds 13-26) exhibited a good antimicrobial activity against Gram posi tive bacteria, with several compounds showing potencies 10-20 times hi gher than 1,2-benzisothiazolin-3-one. None of the chemicals tested inh ibited the growth of E. coli. Yeasts and moulds possess a considerable susceptibility to compounds 12-23. The logP (octanol-water) of esters and amides of N-arylalkanoic and N-aryloxyalkanoic acids were measure d by the shake-flask technique, and the potencies against Gram positiv e bacteria of the compounds tested was related to their lipophilicity. QSAR analysis showed a bilinear relation, with a logD(0) around 3 for the activity on B. subtilis. The phenoxyacetic and phenoxybutyric aci d derivatives are positive outliers, showing a potency higher than tha t predicted from their lipohilicity. The most active compounds were fu rther tested against different Gram positive bacteria and moulds, incl uding Bacilli, Sarcina lutea, Staphylococcus epidermidis, Candida spp. and dermatophytes. The antibacterial and antifungal activity was spec ific for 1,2-benzisothiazolin-3-ones, the corresponding 1,1-dioxide de rivatives being inactive. The genotoxic properties of the compounds st udied were evaluated by the Bacillus subtilis rec-assay and Salmonella -microsome test. None of the compounds showed DNA-damaging or mutageni c activity.