Antiproliferative Bufadienolides from the Bulbs of Drimia altissima.

The bulbs of the South African Drimia altissima (Asparagaceae or Hyacinthaceae sensu APGII) have yielded a range of previously undescribed bufadienolides, drimianins A-G (1-7), the known bufadienolides bovogenin A (8), 3ß-O-ß-d-glucopyranosylbovogenin A (9), scillaren F (10), and altoside (11), the known homoisoflavonoid (3S)-3-(4'-methoxybenzyl)-5,6,7-trimethoxychroman-4-one (urgineanin C), the sesquiterpenoids 1ß,6α-dihydroxy-4(15)-eudesmene and 6α-hydroxy-4(15)-eudesmen-1-one, polybotrin, adenosine, and 9R-hydroxy-(10E,12Z)-octadecadienoic acid ethyl ester. The bufadienolides isolated were tested at 10 µM in the NCI-60 cancer cell screen, and nine of these were selected for further screening at five concentrations. Drimianins C (3) and E (5) showed activity at the nanomolar level against a number of human cancer cell lines in the NCI-60 screen.

The Antiangiogenic Activity of Naturally Occurring and Synthetic Homoisoflavonoids from the Hyacinthaceae ( sensu APGII).

Excessive blood vessel formation in the eye is implicated in wet age-related macular degeneration, proliferative diabetic retinopathy, neovascular glaucoma, and retinopathy of prematurity, which are major causes of blindness. Small molecule antiangiogenic drugs are strongly needed to supplement existing biologics. Homoisoflavonoids have been previously shown to have potent antiproliferative activities in endothelial cells over other cell types. Moreover, they demonstrated a strong antiangiogenic potential in vitro and in vivo in animal models of ocular neovascularization. Here, we tested the antiangiogenic activity of a group of naturally occurring homoisoflavonoids isolated from the family Hyacinthaceae and related synthetic compounds, chosen for synthesis based on structure-activity relationship observations. Several compounds showed interesting antiproliferative and antiangiogenic activities in vitro on retinal microvascular endothelial cells, a disease-relevant cell type, with the synthetic chromane, 46, showing the best activity (GI50 of 2.3 × 10-4 µM).

Phytochemical Investigations of Three Rhodocodon (Hyacinthaceae Sensu APG II) Species.

The genus Rhodocodon (Hyacinthaceae sensu APG II) is endemic to Madagascar, and its phytochemistry has not been described previously. The phytochemistry of three species in this genus has been investigated, and eight compounds, including three bufadienolides (compounds 1, 4, and 5), a norlignan (2), and four homoisoflavonoids (compounds 3 and 6-8), have been isolated and identified. Compounds 1-3 and 6-8 have not been described previously. The COX-2 inhibitory activity of compound 6 and compound 7 acetate (compound 7A) was investigated on isolated colorectal cancer cells. Compounds 6 and 7A inhibited COX-2 by 10% and 8%, respectively, at a concentration of 12.5 µM compared to 12% for 1 mM aspirin (the positive control).

Out of Africa: Miocene dispersal, vicariance, and extinction within Hyacinthaceae subfamily Urgineoideae.

Disjunct distribution patterns in plant lineages are usually explained according to three hypotheses: vicariance, geodispersal, and long-distance dispersal. The role of these hypotheses is tested in Urgineoideae (Hyacinthaceae), a subfamily disjunctly distributed in Africa, Madagascar, India, and the Mediterranean region. The potential ancestral range, dispersal routes, and factors responsible for the current distribution in Urgineoideae are investigated using divergence time estimations. Urgineoideae originated in Southern Africa approximately 48.9 Mya. Two independent dispersal events in the Western Mediterranean region possibly occurred during Early Oligocene and Miocene (29.9-8.5 Mya) via Eastern and Northwestern Africa. A dispersal from Northwestern Africa to India could have occurred between 16.3 and 7.6 Mya. Vicariance and extinction events occurred approximately 21.6 Mya. Colonization of Madagascar occurred between 30.6 and 16.6 Mya, after a single transoceanic dispersal event from Southern Africa. The current disjunct distributions of Urgineoideae are not satisfactorily explained by Gondwana fragmentation or dispersal via boreotropical forests, due to the younger divergence time estimates. The flattened winged seeds of Urgineoideae could have played an important role in long-distance dispersal by strong winds and big storms, whereas geodispersal could have also occurred from Southern Africa to Asia and the Mediterranean region via the so-called arid and high-altitude corridors.

Inferences of biogeographical histories within subfamily Hyacinthoideae using S-DIVA and Bayesian binary MCMC analysis implemented in RASP (Reconstruct Ancestral State in Phylogenies).

BACKGROUND AND AIMS: Subfamily Hyacinthoideae (Hyacinthaceae) comprises more than 400 species. Members are distributed in sub-Saharan Africa, Madagascar, India, eastern Asia, the Mediterranean region and Eurasia. Hyacinthoideae, like many other plant lineages, show disjunct distribution patterns. The aim of this study was to reconstruct the biogeographical history of Hyacinthoideae based on phylogenetic analyses, to find the possible ancestral range of Hyacinthoideae and to identify factors responsible for the current disjunct distribution pattern. METHODS: Parsimony and Bayesian approaches were applied to obtain phylogenetic trees, based on sequences of the trnL-F region. Biogeographical inferences were obtained by applying statistical dispersal-vicariance analysis (S-DIVA) and Bayesian binary MCMC (BBM) analysis implemented in RASP (Reconstruct Ancestral State in Phylogenies). KEY RESULTS: S-DIVA and BBM analyses suggest that the Hyacinthoideae clade seem to have originated in sub-Saharan Africa. Dispersal and vicariance played vital roles in creating the disjunct distribution pattern. Results also suggest an early dispersal to the Mediterranean region, and thus the northward route (from sub-Saharan Africa to Mediterranean) of dispersal is plausible for members of subfamily Hyacinthoideae. CONCLUSIONS: Biogeographical analyses reveal that subfamily Hyacinthoideae has originated in sub-Saharan Africa. S-DIVA indicates an early dispersal event to the Mediterranean region followed by a vicariance event, which resulted in Hyacintheae and Massonieae tribes. By contrast, BBM analysis favours dispersal to the Mediterranean region, eastern Asia and Europe. Biogeographical analysis suggests that sub-Saharan Africa and the Mediterranean region have played vital roles as centres of diversification and radiation within subfamily Hyacinthoideae. In this bimodal distribution pattern, sub-Saharan Africa is the primary centre of diversity and the Mediterranean region is the secondary centre of diversity. Sub-Saharan Africa was the source area for radiation toward Madagascar, the Mediterranean region and India. Radiations occurred from the Mediterranean region to eastern Asia, Europe, western Asia and India.