The effect of several lipid-soluble folic acid antagonists on DNA synthesis in psoriatic and normal skin was studied. The skin samples were incubated in vitro with methotrexate, dichloromethotrexate, and their respective dimethyl esters, followed by exposure to deoxyuridine-3H to assay DNA synthesis radioautographically. Psoriatic epidermal cells were found to be selectively inhibited at lower concentrations (2×10-7M) of these drugs than was normal skin. The ester derivatives were more active than the parent compounds, suggesting that increased lipid solubility of the compounds may potentiate their activity.
Weinstein GD, McCullough JL. Effects of Methotrexate Esters on Normal and Psoriatic Skin. Arch Dermatol. 1975;111(4):471-475. doi:10.1001/archderm.1975.01630160061005