SE309215B - - Google Patents

Abstract

A new antibiotic zedalan is produced by the cultivation of a zedalan-producing strain of Streptomyces achromogenes var. streptozoticus, e.g. NRRL 3125, in an aqueous nutrient medium at a pH of less than 6 under aerobic conditions for a period from 2 to 7 days. Zedalan and streptozotocin, which is also produced, are removed from the culture medium by extraction or adsorption (e.g. on carbon) and then separated, e.g. by countercurrent distribution; because of their different solubilities in water, zedalan is the residue and streptozotocin is in the filtrate, when the material is treated with water and filtered; or they may be separated by chromatography on an alumina column using a C1-C6 alkanol as the eluting agent, the first fractions containing zedalan. Zedalan is an acidic substance which contains C 38.22%, H 4.49%, N 26.74%, O 30.55%; has a M.Wt. and equivalent weight of 157, giving a possible formula of C5H7N3O3; M.Pt. 200 DEG C.; pKa 9.90 in 80% ethanol (acid) v./v., 8.40 in water; it has the I.R. spectrum (in "Nujol"-Registered Trade Mark-mull) in cm.-1 as shown in Fig. 1 and an U.V. spectrum in 95% by volume <PICT:1107632/C2/1> <PICT:1107632/C2/2> aqueous ethanol in mm. as shown in Fig. 2. Zedalan is useful for inhibiting the growth of proliferating neoplastic cells and many therapeutic compositions also containing streptozotocin are described (see Division A5).ALSO:Therapeutic compositions for the treatment of disease conditions due to malignant neoplasms comprise streptozotocin and the new antibiotic zedalan (see Division C2) and a pharmaceutically acceptable carrier. The compositions may be in the form of tablets, capsules, pills, powders, granules, syrups, suspensions or elixirs for oral administration; aqueous and oleaginous compositions for parenteral administration: dusting powders, aerosols, drops (eye and ear), ointments, creams, and lotions for topical application and suppositories. The compositions may also contain anti-neoplastic agents, e.g. busulphan, chlorambucil, cyclophosphamide, mechlorethamine hydrochloride, mercaptopurine, sodium aminopterin, thio-tepa, triethylenemelamine, uracil, fluorouracil and cytosine arabinoside; corticosteroids, e.g. hydrocortisone, prednisolone, 6 a -methylprednisolone and triamcinolone; estrogens, e.g. diethylstilbesterol, progesterone and estradiol: and androgens such as fluoxymesterone, methyltestosterone and testosterone.