Novel, bioactive homoisoflavonoids from a Madagascan Rhodocodon species (Hyacinthaceae, sensu APG II)

Rhodocodon species are endemic to Madagascar and their circumscription has been a topic of debate. Speta [1] treated Rhodocodon as synonymous with Rhadamanthus and Manning [2] included the species in Drimia. Knirsch et al. [3] have recently presented evidence for a separate genus, Rhodocodon. Three novel homoisoflavonoids (compounds 1, 3 and 5) were isolated from the dichloromethane extract of the bulbs of Rhodocodon (Hyacinthaceae, sensu APGII). The structures of these compounds together with the acetates (compounds 2 and 4) were determined by spectroscopic techniques. The absolute stereochemistry at C-3 of compound 5 was determined by circular dichroism and found to be S, unusual for 3-benzyl homoisoflavonoids from the Hyacinthaceae, which are typically R. The effect of compounds 2 – 5 on cyclooxygenase-2 (COX-2) expression in the HCA7 colorectal cancer (CRC) cell line was investigated with compound 3 giving the best result (12% reduction compared to the control). Compounds 2, 3 and 4 were tested for antiangiogenic activity on human retinal microvascular endothelial cells (HREC) and gave GI 50's of 17.6 µM, 17.1 µM and 15.8 µM respectively. Compounds inhibiting angiogenesis are of interest to treat eye diseases characterized by neovascularization of the retina, as well as being of interest as novel anticancer therapies.

References:

[1] Speta F. Hyacinthaceae. In The Families and genera of vascular Plants. Springer, Berlin; 1998: 261 – 285

[2] Manning J C, Goldblatt P, Fay M F. A revised synopsis of Hyacinthaceae in Sub-Saharan Africa, based on molecular evidence, including new combinations and the new tribe Pseudoprospereae. Edinburgh Journal of Botany 2004; 60: 533 – 568

[3] Knirsch W, Martìnez-Azorìn M, Pfosser M, Wetsching W. The reinstatement and rediagnosis of the Madagascan genus Rhodocodon (Asparagaceae, Scilloideae), with validation and remarks on H. perrier's taxa. Phytotaxa 2015; 195: 101 – 133