Ternifoliasaponin, a new triterpenoid saponin from the roots of Gardenia ternifolia Schumach & Thonn (Rubiaceae).

A new triterpenoid saponin, Ternifoliasaponin (1), together with four known compounds (2-5) chikusetsusaponin IVa (2), chikusetsusaponin IVa methyl ester (3), bonushenricoside B (4) and Dianoside C (5) were isolated from roots of Gardenia ternifolia Schumach. & Thonn (Rubiaceae). The structures of isolated compounds were elucidated on the basis of spectroscopic analysis and chemical methods. The antibacterial activities of compounds (3), and (4) were performed by the Muller-Hinton agar diffusion method. The antimicrobial activities of the compounds were studied on Salmonella typhi (Enterobacteriaceae), Staphylococcus aureus and Pseudomonas aeruginosa microorganisms. Compound (3) at 25 mg/mL, showed moderately sensitive effect (8.0 ˂ DIZ ˂14.0 mm) on S. typhi, S. aureus and P. aeruginosa. Compound (4) at 25 mg/mL and compound (3) at 12.5 mg/mL exhibited moderately sensitive effect on S. typhi and S. aureus. Compound (4) inhibited moderately sensitive the S. typhi and P. aeruginosa colonies at 12.5 mg/mL.

Synthesis of some potent immunomodulatory and anti-inflammatory metabolites by fungal transformation of anabolic steroid oxymetholone.

BACKGROUND: Biotransformation of organic compounds by using microbial whole cells provides an efficient approach to obtain novel analogues which are often difficult to synthesize chemically. In this manuscript, we report for the first time the microbial transformation of a synthetic anabolic steroidal drug, oxymetholone, by fungal cell cultures. RESULTS: Incubation of oxymetholone (1) with Macrophomina phaseolina, Aspergillus niger, Rhizopus stolonifer, and Fusarium lini produced 17ß-hydroxy-2-(hydroxy-methyl)-17α-methyl-5α-androstan-1-en-3-one (2), 2α,17α-di(hydroxyl-methyl)-5α-androstan-3ß,17ß-diol (3), 17α-methyl-5α-androstan-2α,3ß,17ß-triol (4), 17ß-hydroxy-2-(hydroxymethyl)-17α-methyl-androst-1,4-dien-3-one (5), 17ß-hydroxy-2α-(hydroxy-methyl)-17α-methyl-5α-androstan-3-one (6), and 2α-(hydroxymethyl)-17α-methyl-5α-androstan-3ß-17ß-diol (7). Their structures were deduced by spectral analyses, as well as single-crystal X-ray diffraction studies. Compounds 2-5 were identified as the new metabolites of 1. The immunomodulatory, and anti-inflammatory activities and cytotoxicity of compounds 1-7 were evaluated by observing their effects on T-cell proliferation, reactive oxygen species (ROS) production, and normal cell growth in MTT assays, respectively. These compounds showed immunosuppressant effect in the T-cell proliferation assay with IC50 values between 31.2 to 2.7 µg/mL, while the IC50 values for ROS inhibition, representing anti-inflammatory effect, were in the range of 25.6 to 2.0 µg/mL. All the compounds were found to be non-toxic in a cell-based cytotoxicity assay. CONCLUSION: Microbial transformation of oxymetholone (1) provides an efficient method for structural transformation of 1. The transformed products were obtained as a result of de novo stereoselective reduction of the enone system, isomerization of double bond, insertion of double bond and hydroxylation. The transformed products, which showed significant immunosuppressant and anti-inflammatory activities, can be further studied for their potential as novel drugs.