Edenharder R, von Petersdorff I, Rauscher R
Institute of Hygiene, University of Mainz, Germany.
Mutat Res. 1993 Jun;287(2):261-74. doi: 10.1016/0027-5107(93)90019-c.
Sixty-four flavonoids were tested for their antimutagenic potencies with respect to IQ in Salmonella typhimurium TA98 and in part also towards MeIQ, MeIQx, Trp-P-2, and Glu-P-1 and in S. typhimurium TA100. Antimutagenic potencies were quantified by the inhibitory dose for 50% reduction of mutagenic activity (ID50). A carbonyl function at C-4 of the flavane nucleus seems to be essential for antimutagenicity: two flavanols and four anthocyanidines were inactive. Again, five isoflavons, except biochanin A, were inactive. Within the other groups of 21 flavones, 16 flavonols and 16 flavanones the parent compounds flavone, flavonol, and flavanone possessed the highest antimutagenic potencies (ID50: 4.1, 2.5, 5.5 nmoles). Increasing polarity by introduction of hydroxyl functions reduced antimutagenic potency. Reducing polarity of hydroxy flavonoids by methyl etherification, however, increased antimutagenic potency again. 6-Hydroxy- and 2'-hydroxy substituted flavonoids were considerably less potent antimutagens. Of 11 flavonoid glycosides tested all compounds except apigenin- and luteolin-7-glucoside (ID50:74, 115 nmoles) were inactive or only weakly antimutagenic. Rings C and A of the nucleus were not essential for antimutagenicity: chalcone and three derivatives were nearly as active as comparable flavones while antimutagenicity of benzylidenacetone was considerably reduced (ID50: 95 nmoles). Cinnamylaldehyde and cinnamoates, however, were inactive. A planar structure in the vicinity of the carbonyl group may also be important for antimutagenicity. Flavanones were less potent antimutagens than the corresponding flavones, but dihydrochalcones and 14 structurally related saturated aromatic carbonyl compounds were inactive. Fisetin and 6-hydroxyflavone were competitive inhibitors, but luteolin was a mixed type inhibitor. The inhibition mechanisms of flavone, kaempferol, morin, flavanone, and 2'-hydroxyflavanone were concentration dependent, being competitive at low concentrations and mixed or non-competitive (2'-hydroxyflavanone) at concentrations about the ID50 value. No fundamental differences between the two tester strains and no clear influence of mutagen structure on antimutagenic potency could be detected.
在鼠伤寒沙门氏菌TA98中，针对IQ测试了64种黄酮类化合物的抗诱变能力，部分化合物还针对MeIQ、MeIQx、Trp-P-2和Glu-P-1进行了测试，同时也在鼠伤寒沙门氏菌TA100中进行了测试。通过使诱变活性降低50%的抑制剂量（ID50）来量化抗诱变能力。黄烷核C-4位的羰基官能团似乎对抗诱变活性至关重要：两种黄烷醇和四种花青素无活性。同样，除了鹰嘴豆芽素A之外的五种异黄酮也无活性。在其他21种黄酮、16种黄酮醇和16种黄烷酮组中，母体化合物黄酮、黄酮醇和黄烷酮具有最高的抗诱变能力（ID50：4.1、2.5、5.5纳摩尔）。通过引入羟基官能团增加极性会降低抗诱变能力。然而，通过甲基醚化降低羟基黄酮的极性又会增加抗诱变能力。6-羟基和2'-羟基取代的黄酮类化合物作为抗诱变剂的效力要低得多。在所测试的11种黄酮苷中，除芹菜素-7-葡萄糖苷和木犀草素-7-葡萄糖苷（ID50：74、115纳摩尔）外，所有化合物均无活性或仅有微弱的抗诱变能力。核的C环和A环对抗诱变活性并非必不可少：查耳酮及其三种衍生物的活性与相应黄酮几乎相同，而亚苄基丙酮的抗诱变能力则大幅降低（ID50：95纳摩尔）。然而，肉桂醛和肉桂酸酯无活性。羰基附近的平面结构对抗诱变活性可能也很重要。黄烷酮作为抗诱变剂的效力低于相应的黄酮，但二氢查耳酮和14种结构相关的饱和芳香羰基化合物无活性。漆黄素和6-羟基黄酮是竞争性抑制剂，但木犀草素是混合型抑制剂。黄酮、山奈酚、桑色素、黄烷酮和2'-羟基黄烷酮的抑制机制与浓度有关，在低浓度时为竞争性抑制，在浓度约为ID50值时为混合型或非竞争性抑制（2'-羟基黄烷酮）。未检测到两种测试菌株之间的根本差异，也未发现诱变剂结构对抗诱变能力有明显影响。
