Studies on the interactions of bioactive quinone avarone and its methylamino derivatives with calf thymus DNA.

The interactions of avarone, a quinone from the marine sponge Dysideaavara, and the methylamino derivatives of avarone (2), 3'-(methylamino)avarone (3) and 4'-(methylamino)avarone (4) with calf thymus DNA (CT-DNA) were studied. Agarose gel electrophoreticanalysis showed that binding of the quinones quenched fluorescence of ethidium bromide (EB). The extent of fluorescence quenching of intercalator EB by competitive displacement from EB-CT-DNA system and of groove binder Hoechst 33258 (H) from H-CT-DNA system with the quinones was analyzed by fluorescence spectroscopy. The obtained results demonstrated that the quinones reduced binding of both the intercalator EB and the minor groove binder H, indicating possible degradation of DNA. The substituent on the quinone moiety determined the extent of DNA damaging effect of the quinone, which was the most extensive with 3'-(methylamino)avarone and the least extensive with its regioisomer 4'-(methylamino)avarone. The results were confirmed by the observed hyperchromic effects in UV-visible spectra measured after interactions of the derivatives with CT-DNA.

Synthesis and biological activity of derivatives of the marine quinone avarone.

Nine alkyl(aryl)thio derivatives of the marine sesquiterpene quinone avarone were synthesized by nucleophilic addition of thiols or thiophenol to avarone. In most cases only one regioisomer was obtained. Their cytotoxic activities, brine shrimp lethality and antibacterial activity were evaluated, as well as those of some previously synthesized avarone derivatives. Anti-HIV activity of two derivatives was tested. Electrochemical properties were determined for all the derivatives in order to obtain more accurate information on structure-activity relationships. Most derivatives showed cytotoxic activity against tumor cell lines, with IC(50) values less than 10 microM for some of them, in particular those with electron-donating substituents. The most active compound was 4'-(methylamino)avarone, with IC(50) value of 2.4 microM to melanoma Fem-X cells, and no cytotoxicity to normal lymphocytes.

Evaluation of the activity of the sponge metabolites avarol and avarone and their synthetic derivatives against fouling micro- and macroorganisms.

The sesquiterpene hydroquinone avarol (1) was isolated from the marine sponge Dysidea avara, whereas the corresponding quinone, avarone (2), was obtained by oxidation of avarol, and the significantly more lipophilic compounds [3'-(p-chloro-phenyl)avarone (3), 3',4'-ethylenedithioavarone (4), 4'-isopropylthioavarone (5), 4'-tert-butylthioavarone (6), 4'-propylthioavarone (7), 4'-octylthioavarone (8)] were obtained by nucleophilic addition of thiols or p-chloroaniline to avarone. All these compounds were tested, at concentrations ranging from 0.5 to 50 microg/mL, for their effect on the settlement of the cyprid stage of Balanus amphitrite, for toxicity to both nauplii and cyprids and for their growth inhibitory activity on marine bacteria (Cobetia marina, Marinobacterium stanieri, Vibrio fischeri and Pseudoalteromonas haloplanktis) and marine fungi (Halosphaeriopsis mediosetigera, Asteromyces cruciatus, Lulworthia uniseptata and Monodictys pelagica).