Cycloviolins A-D, anti-HIV macrocyclic peptides from Leonia cymosa.

Four novel anti-HIV macrocyclic peptides containing 28-31 amino acid residues, named cycloviolins A-D, have been isolated from the hitherto unstudied tropical plant Leonia cymosa. Their primary structure, including amino acid composition and sequence, was determined by a combination of MALDI-TOF and FAB MS and by enzymatic digestion of reduced derivatives, followed by Edman degradation and mass analyses. All of the cycloviolins contain six cysteines, which are present as three intramolecular disulfide bridges. Intriguingly, cycloviolins A-D showed high degrees of sequence homology to the known cyclopsychotride A and circulins A and B from the Rubiaceae family but much less homology to the varv peptides from Viola, a member of the same family (Violaceae).

20-O-beta-glucopyranosyl camptothecin from mostuea brunonis: A potential camptothecin pro-drug with improved solubility.

Bioassay-guided fractionation of the organic extracts of whole plants of Mostuea brunonis (Loganiaceae), using the National Cancer Institute's (NCI) human tumor-based in vitro antitumor screen, led to the isolation and identification of camptothecin 20-O-beta-D-glucoside (1) and three moderately cytotoxic alkaloids, the known deoxypumiloside (2) and strictosamide (3), and the new 2'-O-acetylstrictosamide (4), from the cytotoxic alkaloid fractions. While the previously unknown 20-O-beta-D-glucopyranosyl camptothecin exhibited greater solubility in alcohol, DMSO-H(2)O and H(2)O than camptothecin, it was essentially inactive in the NCI's in vitro 60-cell line primary antitumor screen. However, it could be vulnerable to de-glucosidation in vivo, and may, therefore, merit additional evaluation as a potential prodrug of camptothecin that could be more readily formulated than the parent agent.

HIV-inhibitory and cytotoxic oligostilbenes from the leaves of Hopea malibato.

Three new oligostilbenes, malibatols A (1) and B (2) and dibalanocarpol (3), together with one known oligostilbene balanocarpol (4), were isolated from the organic extract of the leaves of Hopea malibato. The structure elucidation of these compounds was based on the interpretation of their chemical and spectral data. Compounds 3 and 4 exhibited very modest HIV-inhibitory activity, while compounds 1 and 2 were cytotoxic to the host cells (CEM SS) in the antiviral assay.

Compatibility and stability of bryostatin 1 in infusion devices.

Bryostatin 1 is currently in phase II clinical trial sponsored by the National Cancer Institute as an anticancer chemotherapeutic agent. Bryostatin 1 for injection was supplied in a dual pack containing a drug vial and a diluent vial and was manufactured by Ben Venue Laboratories, Inc (Bedford, OH). The stability and compatibility of the bryostatin 1-PET formulation, diluted to 1 and 10 ug/mL in saline and benzyl alcohol preserved saline, with polypropylene (PP) and polyvinyl chloride (PVC) bags at room temperature (27 degrees C) were studied. All experiments were conducted in triplicate and analyses were performed using a validated, stability-indicating, high performance liquid chromatography (HPLC) assay. Bryostatin 1 solutions were compatible with PP bags. At both concentrations and with both salines, the bryostatin content remained unchanged during the 28-day storage period, benzyl alcohol concentration in the preserved saline solutions also remained relatively constant. In PVC bags, however, a decrease in bryostatin 1 concentrations without generation of decomposition products was observed at both dilutions and with both salines during the 28-day storage. A decrease in benzyl alcohol concentration in the preserved saline was also observed. While no diethylhexylphthalate (DEHP) leakage into the solution was observed in PP bags, DEHP leakage in PVC infusion bags was observed on day 2 of storage which increased with storage time and leveled off on day 6. The amount of DEHP leached into drug solution is dependent on the drug concentration. This study suggests bryostatin-PET formulation diluted with preserved saline can be used for long-term (4 week) intravenous administration using PP infusion bags, but not with PVC bags.

Korundamine A, a novel HIV-inhibitory and antimalarial "hybrid" naphthylisoquinoline alkaloid heterodimer from Ancistrocladus korupensis.

A unique heterodimeric naphthylisoquinoline alkaloid, korundamine A (2), comprised of two different monomeric biaryl halves, has been isolated from the Cameroonian tropical liana Ancistrocladus korupensis. Korundamine A is the first "hybrid" dimer found in the Ancistrocladaceae; in vitro, it demonstrated anticytopathic activity against HIV-1 and antimalarial activity against Plasmodium falciparum.

Michellamines D-F, new HIV-inhibitory dimeric naphthylisoquinoline alkaloids, and korupensamine E, a new antimalarial monomer, from Ancistrocladus korupensis.

New monomeric (korupensamine E, 6) and dimeric (michellamines D-F, 7-9) naphthylisoquinoline alkaloids have been isolated from exracts of the tropical liana Ancistrocladus korupensis. Structures were determined by spectroanalytical methods, and stereochemistry was defined through NOE correlations, chemical degradation, and CD spectroscopy. Michellamines D-F exhibited in vitro HIV-inhibitory activity comparable to michellamine B, and korupensamine E exhibited in vitro antimalarial activity comparable to korupensamines A-D.

Triangulynes A-H and trangulynic acid, new cytotxic polyacetylenes from the marine sponge Pellina triangulata.

Nine new polyacetylenes, triangulynes A-H (1-8) and triangulynic acid (9), have been isolated from the marine sponge Pellina triangulata (Oceanapiidae) through cytotoxicity-guided fractionation. Structural elucidations and stereochemistry assignments were based on chemical and spectral studies.

Vasculyne, a new cytotoxic acetylenic alcohol from the marine sponge Cribrochalina vasculum.

A new C43 acetylenic alcohol, vasculyne (1), was isolated by cytotoxicity-guided fractionation of the Caribbean sponge Cribrochalina vasculum. The structure of 1 was determined by spectroscopic methods.

Antitumor activity and stereochemistry of acetylenic alcohols from the sponge Cribrochalina vasculum.

Antitumor bioassay-guided fractionation of the organic extract of the marine sponge Cribrochalina vasculum resulted in the isolation of several closely related cytotoxic acetylenic alcohols [1-8], the structures of which were assigned on the basis of chemical and spectral studies. 3-Hydroxyeicos-(4E)-en-1-yne[1], 3-hydroxydocosa-(4E,15Z)-dien-1-yne[2], 3-hydroxy-16-methyleicos-(4E)-en-1-yne[3], 3-hydroxy-19-methyleicos-(4E)-en-1-yne[4], 3-hydroxy-21-methyldocosa-(4E,15Z)-dien-1-yne [5], and 3-hydroxy-14-methyldocosa-(4E)-en-1-yne [6] are enantiomers of known compounds, while 3-hydroxyheneeicos-(4E)-en-1-yne [7] and 5-hydroxy-16-methyleicos-(3Z)-en-1-yne [8] are new metabolites isolated as minor components. The absolute configuration of C-3 in 1-7 and C-5 in 8 has been assigned as S using the modified Mosher's method. Compounds selected from this series showed selective in vitro antitumor activity against the H-522 non-small cell lung line and the IGROV-1 ovarian line. Synthetic racemic 1 demonstrated a modest dose-related therapeutic activity in a preliminary in vivo xenograft assay based on the latter cell line.