Water soluble salts of fredericamycin A: preparation and biological activity.

logical^ properties of fredericamycin A (FM-A, NSC-305263) a novel antitumor antibiotic produced by Streptomyces griseus (FCRC-48) were reported earlier. The structure (1) was elucidated by spectroscopic and X-ray techniques1'3'4) followed by its biosynthesis,5) electron spin resonance,6) and synthetic studies.n FM-Aexhibited good in vitro activity against Gram-positive bacteria, fungi and was found to be highly cytotoxic in in vitro and in vivo screening.2) Further developmental work could not be carried out to broaden the utility of FMA due to its poor solubility in water and common organic solvents. Chemical modifications of FM-A (acetyl, lauroyl and hydrogenated acetyl derivatives3 >7'8) although slightly improved the solubility in organic solvents, their biological activity was reduced to a great extent compared to FM-A, making them less useful for exploration purposes. More importantly, these derivatives were not water soluble which is an important consideration in preparing formulations for toxicological and clinical studies. The present paper describes the preparation, spectroscopic characterization and the preliminary biological activity of the potassium and sodium salts of FM-A. This is the first report of a water soluble FM-A derivative which retains the high in vitro and in vivo antitumor activity of the parent compound. A critical look at the functional groups of