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Comparative Biological Activity of Seven New Water-soluble Chaulmoogric Acid Derivatives.

1933; SAGE Publishing; Volume: 31; Issue: 2 Linguagem: Inglês

10.3181/00379727-31-7090c

1535-3702

Gladys A. Emerson, Hamilton H. Anderson, Chauncey D. Leake,

Cancer therapeutics and mechanisms

Rogers introduced the first water-soluble chaulmoogra derivative intended for intravenous injection in leprosy, which was recognized to be a systemic disease most rationally treated by administering drugs for systemic effect. Due to the hemolytic, local irritative, sclerosing and other undesirable properties of sodium gynocardate, its intravenous use in humans was generally abandoned even though promising results had been obtained in a considerable number of lepers. No other soluble chaulmoograte has been developed sufficiently free from the disadvantages of “Alepor (sodium hydno-carpate) or sodium gynocardate to warrant its continued intravenous use. This report deals with several compounds which appear from various theoretical considerations to be preferable to the chaulmoogra soaps. Seven new water-soluble derivatives of chaulmoogric acid have been examined pharmacologically and 3 of these have been tested further by a standardized method for antileprotic efficacy as measured by their influence on the course of an experimental leprous infection in rats. The strain of rats, infection, the time and route of administering the drugs, the diet, size of treated and untreated groups, and all other controllable experimental conditions were identical with those used in work previously described. Further experimental treatment is being continued for a more extended period with the more promising agents. In Table I may be found the tolerated and minimum lethal doses on subcutaneous and intravenous injections in rats, the in vitro bactericidal concentration and the effects in experimental rat leprosy of K-iodo-dihydrochaulmoograte (No. 661-K), Na-chaulmoogryl-glycinate (No. 1141) and Na-dichaulmoogryl-β-glycerophosphate (Drug “A”) in comparison with those of “Alepol” (No. 104). The average variations in body weight, size of leprous lesion and incidence of sloughing lesions in each group of infected rats during a 6-months treatment period are included. The toxicity and in vitro bactericidal activity of Na-chaulmoogryl-o-aminobenzoate (No. 1601), diethyl-ethanolammonium chaulmoograte (No. 2001), choline chaulmoograte (No. 2211) and Na-chaulmoogryl glutamate (Drug “B”) are also shown. Summary. On the basis of in vitro bactericidal and hemolytic action, intravenous toxicity, tolerance, and effectiveness in experimental rat leprosy, Na-dichaulmoogryl-β-glycerophosphate (“chaul-phosphate” for convenience), appears superior for possible use in the intravenous treatment of leprosy than other representative water-soluble chaulmoogra derivatives, such as Na-hydnocarpate (“Ale-pol”), K-iodo-dihy dr ochaulmoograte, Na-chaulmoogryl-glycinate, Na-chaulmoogryl-o-aminobenzoate, diethyl-ethanolamrnonium chaul-moograte, and choline chaulmoograte.