Synthesis of angelicin heteroanalogues: preliminary photobiological and pharmacological studies

A series of angelicin heteroanalogues, in which the furan was replaced by t hiophene or a 1-substituted pyrazole moiety, was synthesised in order to ob tain potential therapeutic agents with antiproliferative and/or other biolo gical activities. In general, the antiproliferative activity of the new thi oangelicin, tested in different biological substrates, appeared to be highe r than that of the angelicin, the natural parent compound, but lower than t hat of 8-MOP, the furocoumarin ordinarily used in PUVA therapy and photophe resis. Thioangelicin 6 induced strong inhibition of T2 bacteriophage infect ivity and was able to significantly repress the DNA. synthesis in Ehrlich a scites cells and the clonal growth in HeLa cells. The pyrazolocoumarins did not show any noticeable effect upon UVA irradiation in all the biological systems considered. All the new angelicin heteroanalogues appeared to be fr ee of the known phototoxicity of furocoumarins on the skin. The pyrazolocou marins have also been tested as anti-inflammatory, analgesic, antipyretic, local anaesthetic, anti-arrhythmic and platelet antiaggregating agents by s tandard procedures. In this class of derivatives, 10a showed good anti-infl ammatory and antipyretic properties, while 9a and 11a showed significant lo cal anaesthetic activity. (C) 1998 Elsevier Science S.A. All rights reserve d.