Słoczyńska Karolina, Waszkielewicz Anna Maria, Marona Henryk
Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow, Poland.
Department of Bioorganic Chemistry, Chair of Organic Chemistry, Faculty of Pharmacy, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Krakow, Poland.
Mutat Res Genet Toxicol Environ Mutagen. 2014 Jul 1;768:8-13. doi: 10.1016/j.mrgentox.2014.02.007. Epub 2014 Apr 24.
The Vibrio harveyi assay was used to evaluate mutagenic and anti-mutagenic effects of four new aminoalkanolic derivatives of xanthone with anticonvulsant activity, to select the potentially safe compounds for further in vivo studies in animal models. The study showed that at a concentration of 40 ng/ml the test compounds were not mutagenic. Additionally, two of the investigated compounds, namely the (R,S)-N-methyl-1-amino-2-propanol derivative of 6-methoxyxanthone (compound III) and the (R)-N-methyl-2-amino-1-butanol derivative of 7-chloroxanthone (compound IV) were strong inhibitors of the mutagenicity induced by 4-nitroquinoline-N-oxide (4-NQO) in V. harveyi strains BB7M and BB7XM. The inhibition percentages for compound IV were 49 (in BB7M) and 69 (in BB7XM), whereas for compound III these percentages were 47 (in BB7M) and 42 (in BB7XM), respectively. The present study demonstrates that four bioactive derivatives of xanthone display no mutagenic activity in the V. harveyi assay. In addition, compounds III and IV demonstrated considerable anti-mutagenic activity in this test. Based on the results obtained here, these compounds could be selected for further studies in animal models, while compounds III and IV should be tested further for their anti-mutagenic properties.
哈维氏弧菌试验用于评估四种具有抗惊厥活性的新型呫吨酮氨基链烷醇衍生物的诱变和抗诱变作用,以选择潜在安全的化合物用于动物模型的进一步体内研究。研究表明,在浓度为40 ng/ml时,测试化合物无诱变作用。此外,所研究的两种化合物,即6-甲氧基呫吨酮的(R,S)-N-甲基-1-氨基-2-丙醇衍生物(化合物III)和7-氯呫吨酮的(R)-N-甲基-2-氨基-1-丁醇衍生物(化合物IV),是4-硝基喹啉-N-氧化物(4-NQO)在哈维氏弧菌菌株BB7M和BB7XM中诱导的诱变性的强抑制剂。化合物IV的抑制率在BB7M中为49%,在BB7XM中为69%,而化合物III的抑制率在BB7M中为47%,在BB7XM中分别为42%。本研究表明,四种呫吨酮生物活性衍生物在哈维氏弧菌试验中无诱变活性。此外,化合物III和IV在该试验中表现出相当大的抗诱变活性。基于此处获得的结果,这些化合物可被选择用于动物模型的进一步研究,而化合物III和IV应进一步测试其抗诱变特性。