Propentofylline (PPT, 3-methyl-1-(5-oxohexyl)-7-propyl-xanthine) has been reported to be a beneficial for treatment of both vascular dementia and dementia of the Alzheimer type. PPT was synthesized to increse its solubility in lipids by substituting methyl group with a propyl one in the position 7 of the purine backbone of pentoxifylline. The pharmacological effects of PPT may be exerted via stimulation of the nerve growth factor, increased cerebral blood flow, and inhibition of adenosine uptake. PPT also enhances extracelullar adenosine concentrations and decreases extracellular levels of glutamate in vivo during ischemia.

In contrast to the known pharmacological effects, up to now few clinical pharmacokinetic and metabolism studies of PPT were reported in the literature. The short half-life time of PPT at the terminal elimination phase and poor bioavailability after oral administrations to rabbits suggest that this drug takes the extensive first-pass metabolism in the liver. In vivo it was metabolized to the racemic compound - (±)-1-(5-hydroxyhexyl)-3-methyl-7-propyl-xanthine (HOPPT) [1].

In this work we are presenting the results of stereoselective reduction of PPT to HOPPT catalysed by whole cells of baker^'s and a few strains of wine^'s yeasts in water and in organic solvents. The yeasts for microbiological reduction were carried out under non-fermenting conditions. The stereoselectivity of this biotransformation process was determined using a HPLC with a chiral column. It was stated, that the different yeast strains preferred biotransformation of PPT to the different enantiomers. The wine^'s yeast in the presence of water metabolised PPT to a (R)-3-methyl-1-(5-hydroxyhexyl)-7-propyl xanthine, with the exception of Burgund 38 strain (it formed S-isomer). In this reaction selected baker^'s yeast strains in water and in organic solvents, gave mainly an excess of enantiomer (S) -3-methyl-1-(5-hydroxyhexyl)-7-propyl xanthine. Here the exception was I^'hirondelle strain in n-hexane, which preferred PPT conversion to (R) -isomer.

Acknowledgements:

The research was supported by a scholarship from the Rector^'s Found of the Jagiellonian University.

Authors are grateful to Intervet Company for a free sample of PPT and P. Zamojski for wines yeasts supply.

[1]. Macdonalds C.M., Gebert U., Watson K., Bryce T.A., Omosu M.; Jpn. Pharmacol. Ther., 1986, 14, 31-3.

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