Antimutagenic Activity of a Novel Ascorbic Derivative, Disodium Isostearyl 2-<i>O</i>-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 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 eŠect 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-Nnitrosoguanidine (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 mmol/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 mmol/ml, 0.26 mmol/ml, and 0.17 mmol/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 eŠects against chemical mutagens and UV irradiation.

A review of topical vitamin C derivatives and their efficacy

“…DI‐VCP is a stable, esterified vit C derivative that shares a similar structure with MAP and SAP, but is more lipid‐soluble 3,19 . DI‐VCP appears to have good skin permeability 19 antioxidant activity, antimutagenic effects, and inhibition of melanogenesis 20–23 . Since so few studies have been done on DI‐VCP, and the ones discussed are from the same research group, more data need to be collected to better understand its efficacy.…”

“…A third study showed that topically applied DI‐VCP has greater permeability and skin accumulation than AA or SAP 19 . DI‐VCP was also found to suppress the mutagen‐inducing SOS repair response more than AA and SAP in the umu test, indicating its antimutagenic effects in the presence of UV irradiation and chemical mutagens 22 …”

“…19 DI-VCP was also found to suppress the mutagen-inducing SOS repair response more than AA and SAP in the umu test, indicating its antimutagenic effects in the presence of UV irradiation and chemical mutagens. 22 In vitro and ex vivo experiments indicate that DI-VCP can inhibit melanogenesis in skin, making it a potentially effective skin lightening agent. 23 In cultured human melanoma cells and normal human melanocytes treated with DI-VCP, melanin synthesis decreased to 23% and 52% of non-treated cells, respectfully.…”

Antiestrogenic and antigenotoxic activity of bee pollen from Cystus incanus and Salix alba as evaluated by the yeast estrogen screen and the micronucleus assay in human lymphocytes

“…Also vitamins, which are relatively abundant in pollen samples, can play a role in modulating the genotoxicity induced by the anticancer drugs. For example, it is well known that vitamin C and its synthetic derivatives effectively oppose to chemical mutagens and UV irradiation [48,49].…”