Photochemical and photobiological studies on methylthioangelicins.
4,4',5'-Trimethyl-1'-thioangelicin (1) and 4,6,4',5'-tetramethyl-1'-thioangelicin (2), two newly synthesised isosters of furocoumarins having a sulfur atom in their five-membered ring, were studied in terms of interactions with DNA, both in the ground state and after UVA light absorption. The compounds were able to intercalate the macromolecule and to photobind efficiently, forming C4-cycloadducts with thymine. The antiproliferative effect of this binding was shown in Ehrlich and HeLa cells and by T2 phage inactivation. Tests on Salmonella typhimurium indicated low mutagenic activity. In particular, compound 1 has photobiological activity comparable with that of 4,6,4'-trimethylangelicin, but is less mutagenic.
Miolo
G
G
Department of Pharmaceutical Sciences, University of Padova, Italy. miolo@purple.dsfarm.unipd.it
Caffieri
S
S
Vedaldi
D
D
Baccichetti
F
F
Marzano
C
C
Lucchini
V
V
Rodighiero
P
P
Dall'Acqua
F
F
D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D003374:Coumarins / Q000138:chemical synthesis / Q000494:pharmacology* / Q000528:radiation effects; D003432:Cross-Linking Reagents; D004247:DNA / Q000187:drug effects; D018736:DNA Adducts; D011564:Furocoumarins / Q000138:chemical synthesis / Q000494:pharmacology* / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D013058:Mass Spectrometry; D015394:Molecular Structure; D016296:Mutagenesis / Q000187:drug effects / Q000528:radiation effects; D009153:Mutagens / Q000138:chemical synthesis / Q000494:pharmacology* / Q000528:radiation effects; D017900:Myoviridae / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D018462:Photobiology; D010777:Photochemistry; D010782:Photolysis; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000528:radiation effects; D017382:Reactive Oxygen Species; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects; D013876:Thiophenes / Q000138:chemical synthesis / Q000494:pharmacology* / Q000528:radiation effects
C120223:4,4',5'-trimethyl-1'-thioangelicin; C120224:4,6,4',5'-tetramethyl-1'-thioangelicin; D003374:Coumarins; D003432:Cross-Linking Reagents; D018736:DNA Adducts; D011564:Furocoumarins; D009153:Mutagens; D017319:Photosensitizing Agents; D017382:Reactive Oxygen Species; D013876:Thiophenes; D004247:DNA