BIOLOGICAL PROPERTIES OF SOME BENZOPSORALEN DERIVATIVES |
| |
Authors: | F Bordin F Carlassare M T Conconi A Capozzi F Majone A Guiotto F Baccichetti |
| |
Institution: | Department of Pharmaceutical Sciences, Padua University, Centra di Studio sulla Chimica del Farmaco e dei Prodotti Biologicamente Attivi del CNR, Via Marzolo 5, 35131 Padua, Italy;Department of Biology, Padua University, 35131 Padua, Italy |
| |
Abstract: | Abstract— The biological activity of some benzopsoralen derivatives, prepared with the aim of obtaining new drugs for photochemotherapy, has been studied. The more interesting compounds are 4-hydroxy-methyl-4',5'-benzopsoralen and 4-hydroxymethyl-4',5'-tetrahydro-benzopsoralen, which were found to be active in the dark also: DNA and RNA synthesis were both inhibited in Ehrlich cells, even if in a partially reversible fashion, while protein synthesis remained unaffected. In Chinese hamster ovary cells cultured in vitro , the clonal growth was strongly inhibited by incubation in the dark with both drugs, while a number of chromosomal aberrations was observed in the fraction of growing cells. Using alkaline elution, DNA strand breaks were detected. In addition, in the presence of aphidicolin, a specific inhibitor of DNA polymerase, the clonal growing capacity was completely restored; in contrast, the number of DNA strand breaks remained unchanged. All these results suggest that DNA topoisomerases are probably the target of these two benzopsoralens. These compounds are also good sensitizers; by UV-A irradiation they have a good capacity to produce singlet oxygen, but they appeared to be unable to induce erythemas on guinea-pig skin. Under UV-A light, they induced a strong inhibition of DNA synthesis in Ehrlich cells. Thus, benzopsoralens appear to be capable of inducing strong antiproliferative effects by two different mechanisms, by UV-A irradiation and in the dark. |
| |
Keywords: | |
|
|