Hisama Masayoshi, Matsuda Sanae, Shibayama Hiroharu, Iwaki Masahiro
Central Research Center, Toyo Beauty Co. Ltd., 3-13-8 Higashinakamoto, Higashinari-ku, Osaka, Japan.
Yakugaku Zasshi. 2008 Jun;128(6):933-40. doi: 10.1248/yakushi.128.933.
A novel amphiphilic vitamin C derivative, disodium isostearyl 2-O-L-ascorbyl phosphate (VCP-IS-2Na) possessing an alkyl chain of C(18) to a stable ascorbate derivative sodium L-ascorbic acid 2-phosphate (VCP-Na), was synthesized and evaluated as an anti-mutagen with suppressive effect on SOS-inducing activity on mutagen in the Salmonella typhimurium TA1535/pSK1002 umu test. VCP-IS-2Na was assayed with chemical mutagens, N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), 2-(2-furyl)-3-(5-nitro-2-furyl) acrylamide (furylfuramide) and 4-nitroquinolin 1-oxide (4NQO), which do not require liver metabolizing enzymes. VCP-IS-2Na at a concentration of 0.40 micromol/ml suppressed 66.2%, 54.7% and 60.2% of the SOS-inducing activity on MNNG, furylfuramide, and 4NQO, and the 50% inhibitory dose value (ID(50)) was 0.12 micromol/ml, 0.26 micromol/ml, and 0.17 micromol/ml, respectively. In addition, VCP-IS-2Na was assayed with 2-aminoanthracene (2AA) and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), which require liver metabolizing enzymes. To study the structure-activity relationship, L-ascorbic acid (VC) and VCP-Na were also assayed with all mutagens. VCP-IS-2Na, suppressed the chemical and physical mutagens-induced SOS response greater than VC and VCP-Na in the umu test. Also, the antimutagenic activities of VCP-IS-2Na, VC, and VCP-Na against MNNG and Trp-P-1 were assayed by the Ames test using the S. typhimurium TA100 strain. In summary, this research suggests that VCP-IS-2Na showed potent antimutagenic effects against chemical mutagens and UV irradiation.
一种新型两亲性维生素C衍生物，异硬脂酰2 - O - L -抗坏血酸磷酸二钠（VCP - IS - 2Na），其具有C(18)烷基链，可转化为稳定的抗坏血酸衍生物L -抗坏血酸钠2 - 磷酸（VCP - Na）。在鼠伤寒沙门氏菌TA1535/pSK1002 umu试验中，合成了VCP - IS - 2Na并将其作为抗诱变剂进行评估，其对诱变剂的SOS诱导活性具有抑制作用。使用不需要肝脏代谢酶的化学诱变剂N -甲基 - N' -硝基 - N -亚硝基胍（MNNG）、2 -（2 -呋喃基）- 3 -（5 -硝基 - 2 -呋喃基）丙烯酰胺（呋咱糠酰胺）和4 -硝基喹啉1 -氧化物（4NQO）对VCP - IS - 2Na进行测定。浓度为0.40微摩尔/毫升的VCP - IS - 2Na对MNNG、呋咱糠酰胺和4NQO的SOS诱导活性分别抑制了66.2%、54.7%和60.2%，50%抑制剂量值（ID(50)）分别为0.12微摩尔/毫升、0.26微摩尔/毫升和0.17微摩尔/毫升。此外，使用需要肝脏代谢酶的2 -氨基蒽（2AA）和3 -氨基 - 1,4 -二甲基 - 5H -吡啶并[4,3 - b]吲哚（Trp - P - 1）对VCP - IS - 2Na进行测定。为了研究构效关系，还使用所有诱变剂对L -抗坏血酸（VC）和VCP - Na进行了测定。在umu试验中，VCP - IS - 2Na对化学和物理诱变剂诱导的SOS反应的抑制作用大于VC和VCP - Na。此外，使用鼠伤寒沙门氏菌TA100菌株通过艾姆斯试验测定了VCP - IS - 2Na、VC和VCP - Na对MNNG和Trp - P - 1的抗诱变活性。总之，本研究表明VCP - IS - 2Na对化学诱变剂和紫外线照射显示出强大的抗诱变作用。
