CC-1065 (NSC 298223) is a potent new antitumor antibiotic with a unique structure produced by Streptomyces zelensis. Improved production, isolation, and assay methods are described along with physico-chemical properties and antitumor activity. Screening for soil cultures producing agents displaying both cytotoxic activity against L1210 cells in culture and in vivo activity against P388 leukemia in mice afforded a culture, Streptomyces zelensis, producing a new, potent antitumor antibiotic, CC-1065. Its production, in vitro biological activity, microbiological assays, and taxonomy have already been described1) ; a preliminary communication announced the structure2) shown in Fig. 1. Details of the structure determination have recently been described3). A molecular model of CC-1065 displayed a remarkable curvature, shape,

In a double-blind randomised study, 14 volunteers applied 4% erythromycin plus 1.2% zinc (Zineryt lotion) and 4% erythromycin lotions, each on half of the forehead twice daily for 3 months. The sebum output was evaluated at 3-week intervals using the photometric and the lipid-sensitive film methods. Evaluations of casual level (CL) and sebum excretion rate (SER) were made with a Sebumeter, and total area of lipid spots (TAS) was measured on Sebutapes. Compared to baseline values, the formulation of the erythromycin-zinc complex induced significant reductions in SER after 6 and 9 weeks, and in CL and TAS at 3, 6, 9 and 12 weeks. The mean reduction in TAS was over 20% for four successive 1-h samplings on completion of the study. Significant reductions in CL, SER and TAS were observed for the erythromycin-zinc formulation compared to the control lotion at 6 and 9 weeks, and also at 3 weeks for SER and TAS, and at 12 weeks for CL and TAS. This study indicates that sebum output is significantly reduced by the erythromycin-zinc complex. This reduction is theoretically beneficial for the acneic patient.

SUMMARYCarbon-14 labeled paldimycin trisodium salt was prepared by addition o f N-acetyl-L-cysteine to [14C]paulomycin, the radioactive antibiotic produced by fermentation of Streptomyces ~J U / U S in the presence of L-methionine labeled with carbon-14 in the S-methyl group Carbon-13 nuclear magnetic resonance (NMR) spectra o f paulomycin produced when the fermentation was carried out in the presence o f L-[S-methyl-13Clmethionine showed that isotope incorporation had occurred specifically at the methoxy group of ring C, i.e., the 2-deoxy sugar portion o f paulomycin. With sustained slow feed of labeled precursors during the optimum antibiotic production period, carbon-I4 isotope yields o f up t o 17.5% with specific activity o f up t o 11.4 pCi per milligram o f paulomycin, and carbon-13 isotope yieldsof up t o 24% with 17-fold isotope enrichment over natural abundance, were achieved.