Thienocoumarin derivatives: interaction with nucleic acids and synthetic polydeoxyribonucleotides.
This paper reports the photobiological properties of two new thienocoumarins, 4,6,9-trimethyl-2H-thieno[3,2-g]-1-benzopyran-2-one (compound I) and the 6,9-dimethyl-4-methoxymethyl-2H-thieno[3,2-g]-1-benzopyran-2-one (compound II). Cell growth inhibition studies have revealed significant antiproliferative potency on human tumor cell lines. The photoaddition process of these tritium-labeled derivatives was investigated using various nucleic acid structures (calf thymus DNA, bacterial DNA, and synthetic polydeoxyribonucleotides). The results obtained show that both compounds photobind to DNA to a higher extent than 8-MOP, taken as the reference drug. The capacity to form interstrand crosslinks into DNA helix was also evaluated. Interestingly, notwithstanding the lack of cutaneous phototoxicity, II revealed a good ability to induce diadduct formation.
Gia
O
O
Department of Pharmaceutical Sciences, University of Padova, Italy. gia@dsfarm.unipd.it
Via
L D
LD
Magno
S M
SM
Angelini
G
G
Margonelli
A
A
Rodighiero
P
P
D000818:Animals; D002417:Cattle; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D003374:Coumarins / Q000737:chemistry* / Q000633:toxicity*; D004247:DNA / Q000737:chemistry* / Q000187:drug effects; D004269:DNA, Bacterial / Q000737:chemistry; D018922:HL-60 Cells; D006801:Humans; D007700:Kinetics; D008730:Methoxsalen / Q000633:toxicity; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000633:toxicity*; D011089:Polydeoxyribonucleotides / Q000737:chemistry*; D012867:Skin / Q000187:drug effects* / Q000473:pathology / Q000528:radiation effects; D013876:Thiophenes / Q000737:chemistry* / Q000633:toxicity*; D014407:Tumor Cells, Cultured; D014466:Ultraviolet Rays
C421022:4,6,9-trimethyl-2H-thieno(3,2-g)-1-benzopyran-2-one; C421024:6,9-dimethyl-4-methoxymethyl-2H-thieno(3,2-g)-1-benzopyran-2-one; D003374:Coumarins; D004269:DNA, Bacterial; D017319:Photosensitizing Agents; D011089:Polydeoxyribonucleotides; D013876:Thiophenes; D004247:DNA; D008730:Methoxsalen