Abstract
The in vitro activity of a series of actinonin derivatives against S. aureus has been correlated with free-energy-related substituent parameters by multiple regression analysis. The activity shows a parabolic dependence on partition which probably reflects transport and membrane permeability factors. The relationships also show a dependence on the steric properties of the side-chains and it is suggested that biological activity may be associated with the formation of a tetrahedral transition state at the hydroxamic acid carbonyl group. In vivo activity is poor, possibly because of metabolism to inactive cleavage products.
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