Antimalarial Activity of Prodigiosin

Abstract

SINCE Babès in 1885 claimed the complete inhibition of cholera vibrio by an old culture of Micrococcus prodigiosus there have been numerous descriptions^1–3 of antibiotic properties associated with the bacterium Chromobacterium prodigiosum (Serratia marcescens) and the bipyrrolylpyrrolylmethene prodigiosin (I), which occurs in the red bacterial pigment. The purity of the metabolite^4,5 used in the earlier investigations is suspect and the earlier claims like those for the bacterium lack definition of the true causative factor. In this regard the prodigiosin used has been considered too toxic for therapeutic use, although it has evidently been used in the clinical treatment of some cases of disseminated coccidioidomycosis (San Joaquin Valley fever)⁶. Goble and Boyd⁷ examined a number of porphyrins, bilirubinoids, pyrroles and congeners against Trypanosoma congolese in mice and found chlorophyllins, containing either magnesium or copper, and haematoporphyrin to be effective in delaying death and curative with prolonged treatment. We have investigated the antimalarial properties of purified prodigiosin (I), the cyclotetradepsipeptide serratamolide (II)^4,8,9, an ethyl alcoholic extract of Serratia marcescens (III) from which I, II and other metabolites can be derived⁴, and two dipyrrolylmethenes (IV a and b) against Plasmodium berghei in mice. Prodigiosin showed definite activity (Table 1) against the parasite, which took about twice as long to kill the mice as compared with untreated infections, whereas the other materials exhibited only weak activity at the same or comparable concentrations.