Hirokatsu Nagura

Structure-Activity Relationship of S-Benzylisothiourea Derivatives to Induce Spherical Cells in Escherichia coli

We have previously reported that a novel S-benzylisothiourea derivative, S-(3,4-dichlorobenzyl)isothiourea, tentatively named A22, induced spherical cells in Escherichia coli. To elucidate the structural element(s) required for inducing these spherical cells, the biological activity of S-benzylisothiourea derivatives and related compounds toward E. coli cells was investigated. S-(4-Chlorobenzyl)isothiourea revealed spherical cell-inducing activity, although being slightly less potent than A22, and S-benzylisothiourea itself showed much less activity. S-Cyclohexylmethylisothiourea did not show antibacterial activity and had little effect on the cell shape. S-Heptylisothiourea showed antibacterial activity and induced elongated cells rather than spherical cells. Benzylisothiocyanate inhibited cell growth but did not induce spherical cells. S-Ethylisothiourea, benzylthiocyanate, benzylisocyanate, and N-phenylthiourea did not show any activity under the present experimental conditions. These results indicate that the S-benzylisothiourea structure was necessary and sufficient for inducing spherical cells and that 3- and/or 4-chloro-substitution of the S-benzyl group enhanced this activity.

Structure-Activity Relationship Study of the Bacterial Actin-Like Protein MreB Inhibitors: Effects of Substitution of Benzyl Group in S-Benzylisothiourea

We comprehensively investigated the effects of substitution of the benzyl group in S-benzylisothiourea derivatives on antibacterial activity, because we found previously that some substitutions enhanced it. A 2,4-Cl2-derivative was found to be the most effective compound, it was stronger than the original one in Gram-negative rod shaped-bacteria such as Escherichia coli and Salmonella typhimurium.