2 research outputs found
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Synthesis of isosteric analogues of rooperol
Hypoxoside is a norlignan bisglycoside derived from Hypoxis hemerocallidae (African potato), a medicinal plant used in Africa to treat a variety of disorders, including cancer, cardiac diseases, immune disfunction, inflammation, and prostate hyperplasia. Its aglycone form, (1,5-bis(3’,4’-dihydroxyphenyl)pent-1-en-4-yne (rooperol) is produced in the presence of β-glucosidase which is present in the GI lumen, leading investigators to evaluate hypososide as a potential oral prodrug. Unfortunately, the presence of catechol moieties results in extensive phase II metabolism before therapeutic blood concentrations are achieved. One approach to address this obstacle is to replace the catechols with isosteres which may be more metabolically stable and possess the same bioactivity. This body of work is focused on the synthesis of rooperol and three analogues of rooperol of which the catechol moieties are replaced with a small set of isosteres.Pharmaceutical Science
Scalable Synthesis and Cancer Cell Cytotoxicity of Rooperol and Analogues
Plant polyphenols, such as the African potato (Hypoxis hemerocallidea)-derived bis-catechol rooperol, can display promising anticancer activity yet suffer from rapid metabolism. Embarking upon a program to systematically examine potentially more metabolically stable replacements for the catechol rings in rooperol, we report here a general, scalable synthesis of rooperol and analogues that builds on our previous synthetic approach incorporating a key Pd-catalyzed decarboxylative coupling strategy. Using this approach, we have prepared and evaluated the cancer cell cytotoxicity of rooperol and a series of analogues. While none of the analogues examined here were superior to rooperol in preventing the growth of cancer cells, analogues containing phenol or methylenedioxyphenyl replacements for one or both catechol rings were nearly as effective as rooperol