Synthesis, photobiological activity and photoreactivity of methyl-thieno-8-azacoumarins, novel bioisosters of psoralen.
4,4'-dimethyl-thieno-8-azacoumarin (6) and 4,4',5'-trimethyl-thieno-8-azacoumarin (8) were synthesised. Their photobiological activity was tested on human tumour cell lines. Interestingly, for 6, a photocytotoxic ability higher in HL-60, comparable in HeLa cells, with respect to that of the well-known drug 8-methoxypsoralen (8-MOP), was demonstrated. The covalent photoaddition to DNA occurs by means of the molecular mechanism already demonstrated for furocoumarins. However, it is noteworthy that no skin phototoxicity appears.
Dalla Via
Lisa
L
Dipartimento di Scienze Farmaceutiche, Università di Padova, Padua, Italy. lisa.dallavia@unipd.it
Marciani Magno
Sebastiano
S
Rodighiero
Paolo
P
Gia
Ornella
O
D003374:Coumarins / Q000138:chemical synthesis* / Q000494:pharmacology*; D011564:Furocoumarins / Q000737:chemistry*; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans
C466034:4,4',5'-trimethyl-thieno-8-azacoumarin; C466033:4,4'-dimethyl-thieno-8-azacoumarin; D003374:Coumarins; D011564:Furocoumarins