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)

Bufadienolides and anti-angiogenic homoisoflavonoids from 'Rhodocodon cryptopodus', 'Rhodocodon rotundus' and 'Rhodocodon cyathiformis'

Background: Homoisoflavonoids have been shown to have potent anti-proliferative activities in endothelial cells over other cell types and have demonstrated a strong antiangiogenic potential in vitro and in vivo in animal models of ocular neovascularization. Three species of Rhodocodon (Scilloideaea subfamily of the Asparagaceae family), endemic to Madagascar, R. cryptopodus, R. rotundus and R. cyathiformis, were investigated. Purpose: To isolate and test homoisoflavonoids for their antiangiogenic activity against human retinal microvascular endothelial cells (HRECs), as well as specificity against other ocular cell lines. Methods: Plant material was extracted at room temperature with EtOH. Compounds were isolated using flash column chromatography and were identified using NMR and CD spectroscopy and HRESIMS. Compounds were tested for antiproliferative effects on primary human microvascular retinal endothelial cells (HRECs), ARPE19 retinal pigment epithelial cells, 92–1 uveal melanoma cells, and Y79 retinoblastoma cells. HRECs exposed to compounds were also tested for migration and tube formation ability. Results: Two homoisoflavonoids, 3S-5,7-dihydroxy-(3′-hydroxy-4′-methoxybenzyl)-4-chromanone (1) and 3S-5,7-dihydroxy-(4′-hydroxy-3′-methoxybenzyl)-4-chromanone (2), were isolated along with four bufadienolides. Compound 1 was found to be non-specifically antiproliferative, with GI50 values ranging from 0.21–0.85 μM across the four cell types, while compound 2 showed at least 100-fold specificity for HRECs over the other tested cell lines. Compound 1, with a 3S configuration, was 700 times more potent that the corresponding 3R enantiomer recently isolated from a Massonia species. Conclusion: Select homoisoflavonoids have promise as antiangiogenic agents that are not generally cytotoxic

Linderniaceae Borsch, Kai Mull. & Eb. Fisch.

Linderniaceae on inselbergs in Madagascar <p> Linderniaceae play an important role in the vegetation of granitic or gneissic inselbergs. <i>Linderniella pygmaea</i> (Bonati 1924b: 107) Fischer, Schäferhoff. & Müller (2013: 228) (≡ <i>Craterostigma pygmaeum</i> Bonati) is an endemic species from Central Madagascar (Andringitra massif, Horombe Plateau and Ambatolampy) growing in <i>Coleochloa setifera</i> mats together with <i>Xerophyta dasylirioides</i> Baker (1875: 235), <i>X. pinifolia</i> Lam. ex Poiret (1808: 804) and <i>Pachypodium densiflorum</i> Baker (1887: 503). The species is desiccation tolerant. <i>Linderniella cerastioides</i> (Bonati 1924b: 106) Fischer, Schäferhoff & Müller (2013: 227) (≡ <i>Craterostigma cerastioides</i> Bonati) is also an endemic species restricted to the Andringitra massif and growing in <i>Coleochloa setifera</i> mats on granitic inselbergs accompanied by <i>Xerophyta dasylirioides</i>, <i>X. pinifolia</i> and several succulents (e,g. <i>Pachypodium densiflorum</i>). It is also a desiccation-tolerant taxon. <i>Linderniella horombensis</i> (Fischer 1995: 238) Fischer, Schäferhoff & Müller (2013: 227) (≡ <i>Lindernia horombensis</i> Eb.Fisch.) is another resurrection plant found in <i>Coleochloa setifera</i> mats accompanied by <i>Xerophyta dasylirioides, X. pinifolia</i>, <i>Linderniella pygmaea</i> and several succulents. It is endemic to the Horombe Plateau SW of Ambalavao. The recently described <i>Linderniella porembskii</i> Andriamiar. & Rabarim. in Andriamiarisoa <i>et al.</i> (2023: 12) is morphologically very close to <i>L. horombensis</i> and probably merits only a varietal status. The only other Linderniaceae species endemic to Madagascar, <i>Crepidorhopalon microcarpaeoides</i> (Bonati 1924a: 101) Fischer (1995: 252) (≡ <i>Lindernia microcarpaeoides</i> Bonati), is an annual species occurring in ephemeral flush vegetation in Central Madagascar. Occasionally, the endemic <i>Lindernia lemuriana</i> Fischer, Schäferhoff & Müller (2013: 225) and <i>Lindernia viguieri</i> (Bonati 1926: 3) Fischer (1995: 240), both annual species, are found in ephemeral flush vegetation, but they also occur in anthropogenic habitats like rice fields (Fischer 1995, Fischer 2023). As the inselbergs in Northern Madagascar have not been studied by Rabarimamanarivo <i>et al.</i> (2019), no data on endemic Linderniaceae are available from this area and <i>Lindernia barthlottii</i> is the first record in this region.</p>Published as part of <i>Fischer, Eberhard, Andriantiana, Jacky Lucien & Sieder, Anton, 2023, Lindernia barthlottii (Linderniaceae), a new species from inselbergs in Madagascar, pp. 191-198 in Phytotaxa 626 (3)</i> on page 196, DOI: 10.11646/phytotaxa.626.3.5, <a href="http://zenodo.org/record/10200280">http://zenodo.org/record/10200280</a&gt

Five new species of Rhodocodon (Asparagaceae, Scilloideae) from Madagascar

As part of a taxonomic revision of Rhodocodon, five new species are here described based on distinct syndromes of morphological characters and biogeographical patterns. Rhodocodon petrae resembles R. calcicola but differs in flower morphology and leaf size. Rhodocodon viridans is related to R. intermedius but differs in its proliferous bulb, synanthous leaves, green flowers and long style. Rhodocodon rubescens shows affinities to R. rotundus and R. campanulatus in general appearance but the former shows a different vegetative habit, thicker peduncle, shorter pedicels and larger flowers. Rhodocodon perrieri and R. siederi are related to R. mascarenensis but the two new species differ by the number and morphology of leaves, and flower morphology. A complete morphological description for all new species is provided, including data on biology, ecology and distribution. Furthermore, an identification key for all currently known Rhodocodon species is presented to facilitate future taxonomic work in this genus.This work was also partly supported by the grant ACIE18–03 UAUSTI18–02 from the University of Alicante

Description of Four New Species of Bulbophyllum (Orchidaceae) from Madagascar

Volume: 19Start Page: 344End Page: 35