New potential antitumor compounds from the plant Aristolochia manshuriensis as inhibitors of the CDK2 enzyme.

The 70% aqueous methanolic extract of the Chinese plant Aristolochia manshuriensis was found to contain two novel substituted phenanthrene compounds, SCH 546909 (1), and another phenanthrene glycoside (2). The structures of 1 and 2 were established based on NMR studies. They were identified as inhibitors of the CDK2 enzyme. Compound 1 was found to be a potent inhibitor of the CDK2 enzyme with an IC50 of 140 nM, whereas compound 2 was found to be less active with an IC50 of >10 microM.

Three new compounds from the plant Lippia alva as inhibitors of chemokine receptor 5 (CCR5).

The 70% aqueous methanol extract of the Peruvian plant Lippia alva (Verbenaceae) was found to contain three novel compounds, 1, 2, and 3, which were identified as inhibitors of the chemokine receptor CCR5. The structures of 1-3 were established based on extensive NMR studies. Compounds 1-3 inhibited CCR5 receptor signaling as measured by a calcium mobilization assay with IC(50) values of 5.5, 6.0, and 7.2 microg/mL, respectively.

Two antiviral compounds from the plant Stylogne cauliflora as inhibitors of HCV NS3 protease.

The 70% aq methanolic extract of the Peruvian plant Stylogne cauliflora was found to contain two novel oligophenolic compounds SCH 644343 (1) and SCH 644342 (2), which were identified as inhibitors of HCV NS3 protease. The structure of 1 and 2 was established based on high-resolution NMR studies. Compound 1 inhibited HCV NS3 protease with an IC(50) of 0.3 microM, while compound 2 showed an IC(50) of 0.8 microM.

Novel fungal metabolites as cell wall active antifungals: fermentation, isolation, physico-chemical properties, structure and biological activity.

Two novel antifungals SCH 643432 (1), and 2, were isolated from the fermentation broth of a fungus taxonomically classified as a Paecilomyces varioti. These compounds were separated from the fermentation broth filtrate by adsorption on a macroreticular resin XAD-16 (Amberlite). Purification and separation of the individual compounds were achieved by trituration of the extract with dichloromethane followed by preparative HPLC using reverse phase columns. Extensive FAB (Fast Atom Bombardment) and ESI (Electro Spray) mass spectrometric studies using fragmentation of various daughter ions, NMR experiments and degradative studies helped in elucidating the structure of compound 1. Compound 2 is an isomer of SCH 643432 (1). They were identified as straight chains peptides containing several amino acids such as alanine, aminoisobutyric acid, proline, leucine, glycine and arginine. The N-terminal is terminated in a previously identified beta-keto acid, 2-methyl 3-oxo tetradecanoic acid (MOTDA). Both compounds were active against Candida albicans, other Candidas, dermatophytes and Aspergillus (Geometric Mean MIC's 4.00, 2.59, 3.56, 11.31 and 4.49, 4.00, 5.66, 16.0 microg/ml, respectively for 1 and 2).