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Aims: Drug safety evaluation plays an important role in the early phase of drug development, especially in the preclinical identification of compounds’ biological activity. The Vibrio harveyi assay was used to assess mutagenic and antimutagenic activity of some aminoalkanolic derivatives of xanthone (1–5), which were synthesized and evaluated for their anticonvulsant and hemodynamic activities. Methods and Results: A novel V. harveyi assay was used to assess mutagenic and antimutagenic activity of derivatives of xanthone 1–5. Two V. harveyi strains were used: BB7 (natural isolate) and BB7M (BB7 derivative containing mucA and mucB genes on a plasmid pAB91273, products of these genes enhance error-prone DNA repair). According to the results obtained, the most beneficial mutagenic and antimutagenic profiles were observed for compounds 2 and 3. A modification of the chemical structure of compound 2 by the replacement of the hydroxy group by a chloride improved considerably the antimutagenic activity of the compound. Thus, antimutagenic potency reached a maximum with the presence of tertiary amine and chloride atom in the side chain. Conclusions: Among the newly synthesized aminoalkanolic derivatives of xanthone with potential anticonvulsant properties, there are some compounds exhibiting in vitro antimutagenic activity. In addition, it appears that the V. harveyi assay can be applied for primary mutagenicity and antimutagenicity assessment of compounds. Significance and Impact of the Study: The obtained preliminary mutagenicity and antimutagenicity results encourage further search in the group of amino derivatives of xanthone as the potential antiepileptic drugs also presenting some antimutagenic potential. Furthermore, V. harveyi test may be a useful tool for compounds safety evaluation. [ABSTRACT FROM AUTHOR]

Aim: The biotransformation of pentoxifylline (PTX), propentofylline (PPT) and their racemic hydroxy metabolites ((±)-OHPTX and (±)-OHPPT) by using the fungus Cunninghamella echinulata NRRL 1384. Methods and Results: A fungus Cunninghamella echinulata NRRL 1384 was used to catalyse the ( S)-selective oxidation of the racemic hydroxy metabolites: (±)-OHPTX and (±)-OHPPT and for reduction of PTX and PPT. The first oxidation step appears to be selective and relatively fast while the second reduction step is slower and more selective with PTX. Modifications involving supplementing the bioconversion with glucose give yields and enantiomeric excess (ee) values similar to those obtained without glucose. Conclusions: The bioconversion of (±)-OHPTX gave an ( R)-enantiomer (LSF-lisofylline) with a higher enantiopurity (maximum approximately 93% ee) compared to the bioconversion of (±)-OHPPT, when the maximum ee value for ( R)-OHPPT was recorded at 83%. Significance and Impact of the Study: The conversion of (±)-OHPTX and (±)-OHPPT using Cunninghamella echinulata can be recognized as a process, which may be recommended as an alternative to the methods used to obtain ( R)-OHPTX and ( R)-OHPPT. [ABSTRACT FROM AUTHOR]