Synthetic indole Mannich bases: Their ability to modulate in vitro cellular immunity.

The synthetic indole Mannich bases 1-13 have been investigated for their ability to modulate immune responses measured in vitro. These activities were based on monitoring their affects on T-lymphocyte proliferation, reactive oxygen species (ROS), IL (interleukin)-2, IL-4, and nitric oxide production. Compound 5 was found to be the most potent immunomodulator in this context. Four of the synthesized compounds, 5, 11, 12, and 13, have significant potent inhibitory effects on T-cell proliferation, IL-4, and nitric oxide production. However, none of the thirteen indole compounds exerted any activity against ROS production.

Effect of Grewia asiatica fruit on glycemic index and phagocytosis tested in healthy human subjects.

The Grewia asiatica (commonly known as Phalsa or Fasla) is a shrub or small tree found in southern Asia. It produces purple to black color fruit when ripe. In folk medicine the edible Grewia asiatica fruit is used in a number of pathological conditions. The current study described the effects of Grewia asiatica fruit on glycemic index (GI) and phagocytosis in healthy non-diabetic human subjects. The results showed that Grewia asiatica fruit has low GI value of 5.34 with modest hypoglycemic activity. Luminol-enhanced chemiluminescence assay was carried out to determine the production of reactive oxygen species (ROS) in the oxidative burst activity of whole blood. ROS production was found to be significantly affected, having the 78.3, 58.6 and 30.8% when the subjects were fed with D-glucose, mixture of D-glucose and Grewia asiatica fruit and Grewia asiatica fruit alone respectively as compared to the control. The aqueous, methanolic and butanolic extracts of Grewia asiatica fruits were found to produce a stimulatory effect on ROS production however; the chloroform, hexane and ethanol-acetate extracted exerted significant inhibitory effect. These results demonstrated that Grewia asiatica fruit has desirable effects on blood glucose metabolism manifested as low glycemic response and modulation of ROS production.

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.