Ihstrcrcr:The in vitro antiproliferative activity and in i t v o phototoxicity of some methyl derivatives of ~-methoxypsoraleit ,~n d 5-methoxyangelicin, i.e. 4,4'-dimethyl-5-methoxyangelicin (compound I), 3,4'-dimethyl-5-methoxyangelicin (compound 11). 4,4'-dimethyl-5-methoxypsoralen (compound 111); and 3.4'-dirnethyl-S-methoxypsoralen (compound lV), have been investigated. The effects of the compounds were evaluated in vi/ru on HL60 and A43 I cells, using 5-niethoxypsoralen ; I S the reference compound. In both cell lines compound 1, 11 and 111 showed better antiproliferative activity than coinpound 1V and 5-methoxypsordlen. Scanning electron microscopy revealed [hat all the compounds induced the formation of blebs and blisters on a A431 cell surface. Significant variations in the nuclear area strictly related to the toxicity of the compounds have been shown in both cell lines. Skin Irritancy in viiw was evaluated by mean of histopathological responses on guinea-pig skin. For each compound a damage index was determined by morphometrical analysis of empty spaces in the epidermis. Histopathology revealed skin phototoxicity of compounds which lacked erythemogenic activity by visual ,coring. By coupling cytotoxicity data in virro to skin sensitization ones in viva. compound I proved a promising candidate for use in clinical trials since due to a high inhibitory effect on the growth of human cell lines coupled to low skin phototoxicity.
We analysed the molecular properties of the immunodominant protein of different orf virus strains isolated in Italy. The F1L encoding genes and the deduced amino acid sequences of all strains were determined and compared, and they showed several mutations. Structural analysis was carried out in order to assess the influence of amino acid variations on protein structure demonstrating a conservation of the secondary structure. Western blot analysis and immunogold electron microscopy showed that all orf virus strains were antigenically identical. The results of our study confirmed the immunogenicity of the F1L protein; furthermore, our data suggest a possible involvement of the protein in the virus cycle.
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