Biological activity of a new class of rifamycins Spiro-piperidyl-rifamycins.

Abstract

The biological properties of spiro-piperidyl-rifamycins, a new class of rifamycin antibiotics, are described. In these derivatives the positions 3 and 4 were incorporated into an imidazolyl ring bearing a spiro-piperidyl group N substituted with linear and branched aliphatic chains. The in vitro antibacterial activity against Staphylococcus aureus and Mycobacterium tuberculosis increases with the number of the C atoms in the linear side chain, whereas the inhibitory effect on Escherichia coli is lowered. The antibacterial activity is only marginally affected by branching of the side chain. In vivo (experimental infections of mice) the optimal therapeutic activity against M. tuberculosis is shown by compounds bearing 3-5 C atoms as a linear or branched side chain; in comparison with rifampicin, the potency of these derivatives is 2-3 times higher. The finding is in agreement with the exceptional tissue tropism, which seems to be a favorable property of this group of derivatives.