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PubMed1998

Sequence specific interaction of the antiretrovirally active drug hypericin with 5'ATGGCAGGATAT3' oligonucleotide: a resonance Raman spectroscopy study.

The resonance Raman spectra of two oligonucleotides and their complexes with potent antiretrovirally and antineoplastic active photochemical drug hypericin are reported. The Raman spectra of two oligonucleotides containing twelve base pairs on addition of hypericin (one and two molecules per one oligonucleotide) were compared. The first one contains the first nine base pairs of the "rev" gene coming from HIV genome with three base pairs added to stabilize the duplex (5'ATGGCAGGATAT3') and the second one consists of the same content of the nucleotide bases but in changed sequence order which serves as a control sequence (5'ACGTGATGATGA3'). Differences in the spectra of the "rev" gene sequence and control sequence in interaction with the drug indicate that: i) the AG and GA nucleotide doublets are structurally specific targets for hypericin and ii) the hypericin interaction with 5'AG3' target is stronger than with 5'GA3' one.

Anthracenes↗

PubMed1998

Hypocrellin A photosensitization involves an intracellular pH decrease in 3T3 cells.

The fluorescent pH probe carboxy-seminaphtorhodafluor-1 (C-Snarf-1) has been used for laser microspectro-fluorometric assays of intracellular pH in 3T3 mouse fibroblasts treated with hypocrellin A. These results are compared to those previously obtained with the structurally related hydroxylated polycyclic quinone, hypericin (Sureau et al., J. Am. Chem. Soc. 118, 9484-9487, 1996). A mean local intracellular pH drop of 0.6 units has been observed in the presence of 1 microM hypocrellin A after 90 s of exposure to 0.1 microW of laser irradiation at 514.5 nm. The time evolution of the cytoplasm acidification for hypocrellin A-treated cells is faster than that for cells treated by hypericin. Thus, release of protons from an excited state of hypocrellin A appears to be more efficient than that from hypericin. In addition, the pH dependence of the quenching of C-Snarf-1 fluorescence in 3T3 cells under continuous irradiation has been observed. It is shown here that under continuous illumination, a pH decrease is able to induce a modification of the intracellular binding equilibrium of C-Snarf-1 that results in an increase of C-Snarf-1 fluorescence intensity. This latter observation suggests that the protons generated upon the photoexcitation of hypericin or its analogs may be involved in the production of other photoreactive species. Finally, we suggest that, just as for hypericin, this pH drop may be involved in the antiviral and antitumor activity of hypocrellin A.

3T3 Cells↗