Selective cytotoxicity and apoptosis induction in glioma cell lines by 5-oxygenated-6,7-methylenedioxycoumarins from Pterocaulon species.

The coumarins 5-methoxy-6,7-methylenedioxycoumarin 1 5-(3-methyl-2-butenyloxy)-6,7-methylenedioxycoumarin 2 and 5-(2,3-dihydroxy-3-methylbutyloxy)-6,7-methylenedioxycoumarin 3 isolated from Pterocaulon species showed significant cytotoxicity against two glioma cells lines. Compound 1 presented IC(50) values of 34.6 µM and 31.6 µM against human (U138-MG) and rat (C6) glioma cells, respectively, and this compound was at least two times more potent than compounds 2 and 3. This result could be explained by the planar conformation adopted by 1 through a non-classical hydrogen bond between a hydrogen of the methoxy and the oxygen of the methylenedioxy groups. Another important finding was that the cytotoxic effect induced by 1 in glioma cells was not observed in organotypic cultures, indicating a selective cytotoxicity for tumor cells.

Screening for antiproliferative activity of six southern Brazilian species of Hypericum.

The crude methanolic extracts of six species of Hypericum growing in southern Brazil (Hypericum caprifoliatum Cham. & Schlecht., H. carinatum Griseb., H. connatum Lam., H. myrianthum Cham. & Schlecht., H. polyanthemum Klotzsch ex Reichardt and H. ternum A. St. Hil.) were screened for their antiproliferative activity against two cell lines (HT-29 human colon carcinoma cells and H-460 non-small cell lung carcinoma). The most active crude extracts were those from H. caprifoliatum, H. myrianthum and, to a lesser extent, from H. connatum. All plants were submitted to fractionation with solvents in increasing polarity and re-assayed for the two cell lines used previously, as well as U-373 human malignant glioma cells. The most active fractions were the hexane fractions obtained from H. caprifoliatum, H. myrianthum and H. ternum.

Investigation of some Hypericum species native to Southern of Brazil for antiviral activity.

Three plant species, Hypericum connatum, Hypericum caprifoliatum, Hypericum polyanthemum (Guttiferae), growing in Southern of Brazil were chemically investigated and tested for their antiviral activity against feline immunodeficiency virus (FIV). The chemical analysis revealed the presence of polyphenolic compounds such as tannins and flavonoids. Hypericin was not detected in these species. The aqueous extract (AE), the aqueous extract with low tannin concentration (LTCAE) and the methanolic extract (ME) were tested for their cytotoxic properties in concentrations of 50-150 microg/ml. AE was toxic to CRFK for the three species in all concentrations. LTCAE and ME varied between different concentrations being not toxic or allowing 80% of cell growth. LTCAE and ME (10-50 microg/ml) were analyzed for antiviral activity by inhibition of CPE and measuring FIV genome from cell culture supernatant. LTCAE of all species in this work did not cause any inhibition of FIV. Although no difference was seen in CPE, a lower number of viral particles in the supernatant was observed when FIV infected cells were treated with ME of H. connatum. These results suggest that some plants of the genus Hypericum from Southern Brazil contain compounds with potential antiviral activity against lentiviruses.

Benzopyrans from Hypericum polyanthemum.

From the aerial parts of Hypericum polyanthemum Klotzsch ex Reichardt (Guttiferae), three chromenes, 6-isobutyryl-5,7-dimethoxy-2,2-dimethyl-benzopyran; 7-hydroxy-6-isobutyryl-5-methoxy-2,2-dimethyl-benzopyran and 5-hydroxy-6-isobutyryl-7-methoxy-2,2-dimethyl-benzopyran were isolated. Their structures were determined by NMR spectroscopic analyses.

Genotoxic effect of alkaloids

Because of the increase use of alkaloids in general medical practice in recent years, it is of interest to determine genotoxic, mutagenic and recombinogenic response to different groups of alkaloids in prokaryotic and eucaryotic organisms. Reserpine, boldine and chelerythrine did not show genotoxicity response in the SOS-Chromotest whereas skimmianine showed genotixicity in the presence of a metabolic activation mixture. Voacristine isolated fromthe leaves of Ervatamia coronaria shows in vivo cytostatic and mutagenic effects in Saccharomyces cerevisiae hapioids cells. The Rauwolfia alkaloid (reserpine) was not able to induce reverse mutation and recombinational mitotic events (crossing-over and gene conversion) in yeast diploid strain XS2316.