Biophysical and biological properties of newly synthesized dioxinocoumarin derivatives. II. Dark and photoinduced effects on T7 phage, yeast and HeLa cells.
The dioxinocoumarin derivatives 5H-[2]benzopyrano-[3,4-g][1,4]benzodioxin-5-one (I), 5H-[2]benzopyrano-[3,4-g][2,3]-dihydro-[1,4]benzodioxin-5-on e II, 6H-[2]benzopyrano[3,4-f]-1,4-benzodioxin-6-one (III) and 6H-[2]benzopyrano[3,4-f]-2,3-dihydro-1,4-benzodioxin-6-one (IV) were synthesized. Their biological effect was studied in the presence and absence of UVA radiation, and compared with that of 8-methoxypsoralen (8-MOP) and angelicin derivatives on T7 phage, diploid yeast (Saccharomyces cerevisiae) and HeLa cells. The photobiological activities of compounds I and III were stronger than that of 8-MOP in phage inactivation and DNA synthesis inhibition in HeLa cells, whereas compounds II and IV, with a saturated dioxin ring, showed very poor activity. The photosensitizing activity of dioxinocoumarins on phage inactivation decreased by a factor of two to three in the absence of oxygen. Treatments with compound I and UVA in the presence of oxygen modified the helical structure and stability of phage DNA and proteins. Compounds I and II were more active than IV for photoinduced cell killing in yeast, although always less active than 8-MOP. At comparable photocytotoxic levels, compounds I and III were as strong inducers of cytoplasmic "petite" mutants in yeast as angelicin, suggesting a possible monofunctional mode of action with cellular DNA.
Csík
G
G
Institute of Biophysics, Semmelweis University of Medicine, Budapest, Hungary.
Rontó
G
G
Nocentini
S
S
Averbeck
S
S
Averbeck
D
D
Besson
T
T
Coudert
G
G
Guillaumet
G
G
D000332:Aerobiosis; D000693:Anaerobiosis; D017123:Bacteriophage T7 / Q000187:drug effects* / Q000528:radiation effects; D003374:Coumarins / Q000138:chemical synthesis / Q000633:toxicity*; D004261:DNA Replication / Q000187:drug effects / Q000528:radiation effects; D004279:DNA, Viral / Q000737:chemistry / Q000187:drug effects / Q000528:radiation effects; D003624:Darkness; D004146:Dioxanes / Q000138:chemical synthesis / Q000633:toxicity*; D004307:Dose-Response Relationship, Radiation; D004926:Escherichia coli; D011564:Furocoumarins / Q000633:toxicity; D006367:HeLa Cells; D006801:Humans; D007202:Indicators and Reagents; D007364:Intercalating Agents / Q000633:toxicity; D008027:Light; D008730:Methoxsalen / Q000633:toxicity; D015394:Molecular Structure; D017319:Photosensitizing Agents / Q000633:toxicity*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000528:radiation effects; D013329:Structure-Activity Relationship; D014466:Ultraviolet Rays
D003374:Coumarins; D004279:DNA, Viral; D004146:Dioxanes; D011564:Furocoumarins; D007202:Indicators and Reagents; D007364:Intercalating Agents; D017319:Photosensitizing Agents; C011659:angelicin; D008730:Methoxsalen