PHOTOBIOLOGICAL PROPERTIES OF 1'-THIENO-4,6,4'-TRIMETHYLANGELICIN

Some photobiological properties of 1'-thieno-4,6,4'-trimethylangelicin (TTMA), a new isoster of 4,6,4'-trimethylangelicin (TMA) were studied in comparison with the parent compound. The TTMA absorbs UVA light an d photobinds in vitro to DNA more efficiently than TMA; however, in Eh rlich cells in vivo TTMA linked to DNA to a lesser extent than the par ent compound, In general, the formation of damage into DNA is in line with this last result: In fact, TTMA and TMA form equivalent amounts o f interstrand cross-links (ISC) both in vitro in linearized PM2 DNA an d in vivo in HeLa cells, In this system TTMA induces DNA-protein cross -links (DPC) more efficiently than TMA; on the contrary, no significan t amounts of single-strand breaks were detected with both compounds, T he antiproliferative activity of TTMA is consistent with these results , being only slightly more pronounced than that of TMA, Experiments ca rried out using double irradiation demonstrated that these drugs are c apable of inducing antiproliferative effects by biphotonic reactions, including the formation of both TSC and DPC. Thus, replacement of the oxygen atom by a sulfur increases the UV absorption of the drug and it s capacity to photobind to DNA irt vitro but does not yield a comparab le enhancement of its photosensitizing properties in vivo; this might be due to various reasons, for instance to an increase in the lipophil ic character that could modify the behavior in vivo.