Antimutagenic activity of a novel ascorbic derivative, disodium isostearyl 2-O-L-ascorbyl phosphate

Abstract

A novel amphiphilic vitamin C derivative, disodium isostearyl 2-O-L-ascorbyl phosphate (VCP-IS-2Na)possessing an alkyl chain of C18 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 μmol/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(ID50)was 0.12 μmol/ml, 0.26 μmol/ml, and 0.17 μmol/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. © 2008 The Pharmaceutical Society of Japan.