Effect of cryptolepine on some enterobacteriaceae and possible mechanism of action of cryptolepine

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Some members of the Enterobacteriaceae were treated with cryptolepine hydrochloride and varying degrees of growth inhibition was observed. Escherichia coil (NCTC 5933) and laboratory strains of Shigella dysenteriae, Proteus vulgaris, Klebsieila pneumoniae and Salmonella typhii were all inhibited by the drug. Proteus vulgaris showed the greatest sensitivity (MIC 32.67 µg/ml) and Shigella dysenteriae the least (MIC 76.22µg/ml). The action appeared to be bacteriostatic in all cases. When cryptolepine hydrochloride was added to exponentially growing E. coil cells the turbidities of the suspensions decreased sharply over the first 24 hour period. Thereafter there was a gradual decrease in turbidity. Increasing the concentration of drug to double the MIC brought about a sharper/steeper fall in optical density of the medium over the 24 hour period. Increasing concentration to three (3) times the MIC however did not produce any appreciable drop in optical density. Addition of Cryptolepine hydrochloride to heat-killed (60°C for 30 minutes) E. coli cultures did not cause a decrease in turbidity. Cryptolepine appears to interfere with the osmotic barrier in the bacteria thus allowing the leakage of minute quantities of some intracellular cell components into the culture medium. Chrornatographic analysis of drug-treated culture suspensions appear to indicate that some nucleotide(s) and perhaps other components are released from the bacterial cells under the action of cryptolepine. A component with Rf value closely resembling that of a purine was seen on chromatograms of drug-treated cultures run in n-Butanol: Water: NH3 solvent system. When both drug-treated and drug-free E. coli cells were observed under the phase contrast microscope there were some distortions in the protoplast membrane (and perhaps even the cell wall) of the cryptolepine-treated E. coli cells. This appears to suggest that cryptolepine causes some kind of damage to the cell barriers (membranes, walls etc). This damage which may be permanent or transient results in alteration of the permeability characteristics of the cell membranes under the influence of the drug thus allowing the leakage of cell components into the culture medium. Cryptolepine hydrochloride interacts indifferently towards am ampicillin, streptomycin and gentamycin, that is, the two sets of drugs act together with neither antagonism nor potentiation.
A thesis submitted to the College of Health Sciences in partial fulfillment of the Requirements of the Degree of Master of Pharmacy, 1992