Seven derivatives of 6-chloro-2-quinoxalinecarboxylic acid 1, 4-dioxide were prepared. These include esters, amides and the acid hydrazide. The derivatives were tested against fifteen bacteria by agar diffusion assay and against two bacterial infections in vivo. Increased effectiveness on oral administration was observed with the carboxamide.
Mycophenolic acid shows significant antitumor activity against several strains of transplantable mouse tumors, some of which were originally established as syngeneic in tumor-host realtionship. Mycophenolic acid was more effective against solid than ascitic tumors. Oral, subcutaneous or intraperitoneal administration was equally effective.
A new pigment antibiotic named chrothiomycin, which inhibits the growth of some Gram-positive bacteria and the enzymic activities of oxygenases involved in catecholamine biosynthesis in vitro, was isolated from fermentation broths of Streptomyces pluricolorescens. It is obtained as blackish purple crystals, C27H31-33O13NS.
1'-Demethylclindamycin was produced by N-demethylation when clindamycin was added to fermentations of Streptomyces punipalus. In contrast, addition of clindamycin to fermentations of Streptomyces armentosus resulted primarily in the production of clindamycin sulfoxide. Several other species of streptomycetes as well as several species of fungi were also found to convert clindamycin to either 1'-demethylclindamycin, clindamycin sulfoxide, or a mixture of both compounds.
The effects of various tumor-inhibitory antibiotics on immunological responses were investigated, using serum antibody production against human gamma globulin and sheep red cells in mice, development of tuberculin hypersensitivity in guinea pigs, and skin allograft reaction in mice. The effects on antibody-forming cells in the mouse spleen were observed by JERNE'S method. Of the antibiotics examined, pluramycin significantly suppressed the immunological responses. The responses of cellular antibodies were more markedly affected than those of circulating antibodies. By the method employed, bleomycin, phenomycin, angustmycins A and C did not exhibit any significant activity of immunosuppression. The skin allograft reaction was not significantly modified by formycins A and B. Pluramycin was observed to inhibit the growth of plasmocytoma in mice.
A new antibiotic, oryzachlorin, C26H31O8N2S2Cl(λmax 298mμ in ethanol) has been isolated from Aspergillus oryzae. It strongly inhibits the growth of many yeasts but has no effect on bacteria or filamentous fungi. It also has antiviral activity in vitro.
The proton magnetic resonance spectra of some erythromycin aglycones have been investigated at 100MHz in both deuteriochloroform and pyridine-d5 solvents. Utilizing information derived from pyridine solvent Δ-values (Δ= δCDCl3-δC5D5N) and spin-spin coupling constants for vicinal protons, the preferred approximate conformations of these 14-membered lactone ring systems in solution have been shown to be the same in III, IV, V and VI and to closely approximate the conformation previously derived from X-ray analysis for the aglycone ring in erythromycin A. The asymmetry at C-9 in dihydroaglycones IV, V and VI has been shown to be S in V and VI and R in IV. The utility of pyridine solvent shifts in the three-dimensional analysis of hydroxylic compounds is uniquely demonstrated in these polyhydroxy macrolides and emphasizes the potential of this technique for structure analysis.