Study of the Phototoxic Effect of the Novel Substituted Derivatives of Furodihydroquinoline, Putative Medicines for Phototherapy of Psoriasis

摘要

Previously, a method of synthesis of trimethyl-substituted furodihydroquinoline (FDHQ), a putative photosensitizer for the therapy of psoriasis, was disclosed in patent RU #2614248. FDHQ was proposed for substituting derivatives of the psoralen (8-methoxypsoralen, 8-MOP; 5-methoxypsoralen, 5-MOP; and trimethylpsoralen, TMP) actually applied for this purpose. FDHQ exhibited an advantage over psoralens in safety for the patient. However, practical use of FDHQ was found to be impossible due to its insufficient solubility in any clinically permitted solvents. To solve this problem, a synthesis of six earlier unknown derivatives of FDHQ with side substitutes in position 5 of the benzene nucleus (carbamate, acetamide, and sulfuric moieties) were synthesized: N-(6,8,8-trimethyl-8,9-dihydrofuro[3,2-h]quinoline-5-yl)acetamide (W); tert-butyl (6,8,8-trimethyl-8,9-dihydrofuro[3,2-h]quinoline-5-yl)carbamate (K); tret-butylacetyl (6,8,8-trimethyl-8,9-dihydrofuro[3,2-h]quinoline-5-yl)-carbamate (WK); N-methyl-N-(6,8,8-trimethyl-8,9-dihydrofuro[3,2-h]quinoline-5-yl)acetamide (WC1); N-octyl-N-(6,8,8-trimethyl-8,9-dihydrofuro[3,2-h]quinoline-5-yl)acetamide (WC8); sodium acetyl (6,8,8-trimethyl dihydrofuro[3,2-h]quinoline-5-yl)sulfamate (S). In vitro testing on T-cell lympholeukosis (Jurkat), B-cell lymphoma (Raji) cell lines and immortalized human fibroblasts demonstrated optimal photosensitizing properties in compound S. The ratio between dark toxicity and phototoxicity of this compound (irradiation with UV light with lambda = 302 nm) on the chosen model cell lines suggests it as a putative efficient and safe medicine for phototherapy of psoriasis.