Antimutagenic activity of a novel ascorbic derivative, disodium isostearyl 2-O-L-ascorbyl phosphate.
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.
Hisama
Masayoshi
M
Central Research Center, Toyo Beauty Co. Ltd., 3-13-8 Higashinakamoto, Higashinari-ku, Osaka, Japan. hisama@toyobeauty.jp
Matsuda
Sanae
S
Shibayama
Hiroharu
H
Iwaki
Masahiro
M
D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D002243:Carbolines; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D008769:Methylnitronitrosoguanidine; D016296:Mutagenesis / Q000187:drug effects* / Q000528:radiation effects; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens; D012486:Salmonella typhimurium / Q000235:genetics* / Q000528:radiation effects; D014466:Ultraviolet Rays / Q000009:adverse effects
D002243:Carbolines; D009153:Mutagens; D008769:Methylnitronitrosoguanidine; C528521:disodium isostearyl 2-O-L-ascorbyl phosphate; C019132:3-amino-1,4-dimethyl-5H-pyrido(4,3-b)indole; D001205:Ascorbic Acid