Evaluation of mutagenic and antimutagenic properties of some bioactive xanthone derivatives using Vibrio harveyi test

• Published in: Letters in applied microbiology Vol. 50; no. 3; pp. 252 - 257
• Main Authors: Słoczyńska, K, Pękala, E, Wajda, A, Węgrzyn, G, Marona, H
• Format: Journal Article
• Language: English
• Published: Oxford, UK Oxford, UK : Blackwell Publishing Ltd 01.03.2010; Blackwell Publishing Ltd; Blackwell
• Subjects: 4-nitroquinoline-N-oxide; Anticonvulsants - chemical synthesis; Anticonvulsants - chemistry; Anticonvulsants - pharmacology; antimutagenic activity; Antimutagenic Agents - chemistry; Antimutagenic Agents - pharmacology; Biological and medical sciences; DNA Repair; Drug Evaluation, Preclinical; Fundamental and applied biological sciences. Psychology; Microbiology; mutagenicity; Mutagenicity Tests; Mutagens - chemistry; Mutagens - pharmacology; Vibrio - drug effects; Vibrio - genetics; Vibrio harveyi; Vibrio harveyi assay; xanthone derivatives; Xanthones - chemistry; Xanthones - pharmacology; xanthone derivatives; mutagenicity; Vibrio harveyi; Vibrio harveyi assay; antimutagenic activity; Applied microbiology; Bacteria; Vibrionaceae; 4-nitroquinoline-N-oxide; Mutagen
• ISSN: 0266-8254; 1472-765X
• DOI: 10.1111/j.1472-765X.2009.02781.x

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. 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. 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. 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.