TL;DR: The results suggest that repair replication in response to 8-MOP is primarily a response to monoadducts and that the enzymatic pathway for this repair synthesis shares at least one step with the pathway for repair of pyrimidine dimers.
Abstract: Photoactivated 8-methoxypsoralen (8-MOP) has been proven to be clinically effective for a number of dermatological conditions including lichen planus, mycosis fungoides, and psoriasis. 8-MOP forms two types of covalent photoproducts with DNA, monoadducts, and bifunctional adducts which crosslink the two DNA strands. Angelicin is a congener of 8-MOP which forms only monoadducts. We have used the combined density and isotopic labeling technique to study repair replication in cultured human fibroblasts treated with either of these compounds and exposed to near-ultraviolet light. In human diploid fibroblasts (WI-38), the time course of repair replication for both compounds is similar. Drug concentration and ultraviolet dose responses are also similar for 8-MOP and angelicin. No repair replication was stimulated by either compound in xeroderma pigmentosum cells from Complementation Group A (XP12BE). These results suggest that repair replication in response to 8-MOP is primarily a response to monoadducts and that the enzymatic pathway for this repair synthesis shares at least one step with the pathway for repair of pyrimidine dimers. Cross-link persistence in treated cells was assayed by use of the single-strand-specific S1 nuclease to digest DNA that did not renature readily following heat denaturation. Partial removal of cross-links was observed in normal, xeroderma pigmentosum variant, and Fanconi9s anemia fibroblasts, but not in xeroderma pigmentosum Group A cells.
TL;DR: Preliminary mechanistic studies suggest that these compounds act as anti-influenza agents by inhibiting ribonucleoprotein (RNP) complex associated activity and have the potential to be developed further, which could form the basis for developing additional defense against influenza pandemics.
Abstract: By using a cell-based high throughput screening campaign, a novel angelicin derivative 6a was identified to inhibit influenza A (H1N1) virus induced cytopathic effect in Madin-Darby canine kidney cell culture in low micromolar range. Detailed structure-activity relationship studies of 6a revealed that the angelicin scaffold is essential for activity in pharmacophore B, while meta-substituted phenyl/2-thiophene rings are optimal in pharmacophore A and C. The optimized lead 4-methyl-9-phenyl-8-(thiophene-2-carbonyl)-furo[2,3-h]chromen-2-one (8g, IC(50) = 70 nM) showed 64-fold enhanced activity compared to the high throughput screening (HTS) hit 6a. Also, 8g was found effective in case of influenza A (H3N2) and influenza B virus strains similar to approved anti-influenza drug zanamivir (4). Preliminary mechanistic studies suggest that these compounds act as anti-influenza agents by inhibiting ribonucleoprotein (RNP) complex associated activity and have the potential to be developed further, which could form the basis for developing additional defense against influenza pandemics.
TL;DR: It is concluded that at least two xanthotoxin-inducible P450s from highly divergent subfamilies (CYP6B and CYP321A) contribute to the resistance of H. zea larvae to toxic furanocoumarins and insecticides.
TL;DR: The efficient reactions also found for psoralen and angelicin triplets with amino acids suggest that such triplets in vivo may also react with these components, and significant damage may thus be caused to protein as well as nucleic acid components of the cell.
Abstract: . The triplet-triplet absorption spectra of psoralen, xanthotoxin, angelicin and bergapten have been determined using the technique of pulse radiolysis and laser flash photolysis in benzene and water. The extinction coefficients of the triplet transitions have been measured and used to determine the singlet → triplet intersystem crossing quantum yields for 353 nm excitation. These yields vary considerably in passing from benzene to water as solvent. The highest yields were obtained for psoralen and angelicin in water, being 0.45 and 0.33, respectively. Reaction rate constants of the psoralen and angelicin triplets with various pyrimidine and purine nucleic acid bases and amino acids have been measured. The high reactivities support the suggestion that the photosensitising properties of furocou-marins are mediated by the corresponding furocoumarin triplet states. The similarly high S → T quantum yields, and triplet reactivities with pyrimidines of psoralen and angelicin, also support the suggestion that the observed differences in photosensitising properties of these two psoralens may be due to their differing geometries, which allow psoralen itself to intercalate DNA more easily than angelicin. The efficient reactions also found for psoralen and angelicin triplets with amino acids suggest that such triplets in vivo may also react with these components. Significant damage may thus be caused to protein as well as nucleic acid components of the cell.
TL;DR: Psoralidin, bakuchicin, psoralin and angelicin isolated from the seeds of Psoralea corylifolia showed significant antibacterial activities against a number of Gram + and Gram (-) bacteria.