CRYPTOLEPINE HYDROCHLORIDE EFFECT ON STAPHYLOCOCCUS-AUREUS

Staphylococcus aureus cultures treated with the hydrochloride salt of the indoquinoline alkaloid, cryptolepine, which was isolated from the roots of Cryptolepis sanguinolenta, showed biphasic steady‐state generation curves at the same dose level. The apparent generation rate constant for the initial phase of action (phase I) was greater than that for phase II. The formal dependence of the apparent generation rate constant on drug concentration for the phase I action was linear at low drug concentrations but asymptotically approached zero at high concentrations, indicating saturation of the receptor sites engaged in microbial protein synthesis. The dependence for phase II action was linear in the entire concentration range and demonstrated a process that did not conform to a saturable receptor site model but resulted in a kill or lysis of the cells. Cryptolepine possesses bacteriostatic and bactericidal actions. Both phenomena occur in the initial stages of drug‐bacteria reaction, but the bactericidal action predominates in subsequent stages. The effects of pH changes in broth media on generation inhibition of S. aureus by cryptolepine hydrochloride action indicated that the unprotonated drug fraction contributes to its activity, possibly because of its ready penetration through the cell membrane. Copyright © 1979 Wiley‐Liss, Inc., A Wiley Company