New furobensopyrones as possible agents for the photochemotherapy of psoriasis with expected monofunctional mode for DNA

ABSTRACT

This work involved the synthesis of linear furobenzopyrone analogs as monofunctional photochemotherapeutic agents, aiming to obtain compounds with increased activity and reduced toxicity. A rough investigation was carried out on the conformation of a new bulky substituent like phenyl group in the furobenzopyrone system to produce compounds that could react with DNA in a monofunctional sense, therefore reducing or eliminating skin phototoxicity or the risk of skin cancer and, at the same time, maintaining the same selectivity of action as psoralen, [linear furobenzopyrone]. So, they have synthesized linear furobenzopyrone derivatives [3a-c and 8a1-6], in which methyl and phenyl groups were systematically varied at the 2, 3, 5, and 9 positions. Preliminary screening for the photosensitizing activity of some of the new analogs have revealed that compound [8a1] is more active as photosensitizer than xanthotoxin [reference], while 3b, c and 8a4-6 are less active. In addition, 3a and 8a2-3 showed no photosensitizing activity