Extracts of marine species from Baja California and theCaribbean have been examined on shipboard for a variety of bioactlvities and their constituents studied there by gas chromatography! mass spectrometry. A very high proportion of the extracts has been shown to be cytotoxic, a high proportion to be antibacterial or antifungal and a surprisingly large number to be antiviral. Many of these activities have been confirmed in more extensive assays against tumor cells, pathogenic microorganisms and a battery of viruses. A number of the compounds responsible for the activities have been identified, including several new compounds. Of special current interest are the didemnins, depsipeptides isolated from a didemnid tunicate, which inhibit a number of RNA and DNA viruses and exhibit potent cytotoxicity vs. tumor cell lines.

Trospectomycin (U-63366F) is a novel spectinomycin analog with broad-spectrum antibacterial activity. The in vitro activity of this analog was compared with that of spectinomycin and other reference antibiotics against 411 clinical isolates of aerobic and anaerobic bacteria. MICs were determined by agar or broth dilution methods. The stability of trospectomycin in the presence of an enzyme extract derived from spectinomycinresistant Escherichia coli was determined. Trospectomycin was more active than spectinomycin (4-to 32-fold) against strains of numerous bacterial species, including staphylococci, streptococci, Haemophilus influenzae, Branhamella catarrhalis, Neisseria gonorrhoeae, Proteus species, Bacteroides species, Clostridium difficile, Clostridium species, and Chlamydia trachomatis. Trospectomycin demonstrated a moderate level of activity (comparable to that of spectinomycin) for most species of the family Enterobacteriaceae tested and was generally cross resistant with spectinomycin. Trospectomycin was susceptible to inactivation by crude enzyme preparations from spectinomycin-inactivating strains of E. coli. Trospectomycin inhibited a variety of clinically important organisms, including agents of sexually transmitted diseases and pelvic inflammatory disease. Clinical studies with this novel aminocyclitol antibiotic are in progress.Spectinomycin is an aminocyclitol antibiotic with broadspectrum antibacterial activity (9). Spectinomycin is not an aminoglycosidic aminocyclitol and has never exhibited the oto-or nephrotoxicity associated with that antibiotic group (15, 16). The antibiotic achieves high levels in animal and human serum and urine and has been used successfully to treat a variety of infections (10, 24). However, it is generally less active in vitro than the aminoglycosides and has been used primarily for the treatment of uncomplicated anogenital gonorrhea, including penicillin-resistant gonorrhea (17). Spectinomycin is not indicated for the treatment of infections due to Chlamydia trachomatis or Treponema pallidum.Chemical analogs of spectinomycin were prepared in an attempt to enhance the potency of spectinomycin or expand its antimicrobial spectrum. Structural changes in the cyclitol portion (A-ring; Fig. 1) of the molecule result in a loss of bioactivity (18). Synthetic methods developed in The Upjohn Company laboratories have afforded the opportunity to modify the previously inaccessible C-ring portion of the molecule to yield 3'-and 6'-modified spectinomycin analogs (22,28 177, 1982). The 6' analogs are generally superior in antimicrobial activity to the 3' analogs. When compared with spectinomycin in vivo, the 6' analogs are 2-to 50-fold more potent than spectinomycin against Haemophilus influenzae, Streptococcus pyogenes, and Salmonella spp. (C. W. Ford, J. C. Osinski, G. E. Zurenko, and R. J. Yancey, Jr., 22nd ICAAC, abstr. no. 178, 1982). Of the analogs tested, 6' propylspectinomycin sulfate pentahydrate (trospectomycin sulfate or U-63366F) (Fig. 1) has been judged to possess the gr...

The effects of subinhibitory concentrations of antibiotics on polymorphonuclear leukocyte (PML) and serum killing of Staphylococcus aureus 502A (UC 9116) and Escherichia coli UC 9451 were studied. Exposure of these bacteria to subinhibitory levels of certain lincosaminides, spectinomycin, or 6'-n-propylspectinomycin altered their susceptibility to these host defense mechanisms, while exposure to gentamicin had no effect. However, each organism responded differently to treatment with the antibiotics.S. arrreus pretreated during log

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