Research Progress of Polycyclic Polyprenylated Acylphloroglucinols

Abstract

Polycyclic polyprenylated acylphloroglucinols (PPAPs) are a class of hybrid natural products sharing the mevalonate/methylerythritol phosphate and polyketide biosynthetic pathways and showing considerable structure and bioactivity diversity. This review discusses the progress of research into the chemistry and biological activity of 421 natural PPAPs in the past 11 years as well as in-depth studies of biological activities and total synthesis of some PPAPs isolated before 2006. We created an online database of all PPAPs known to date at http://www.chem.uky.edu/research/grossman/PPAPs . Two subclasses of biosynthetically related metabolites, spirocyclic PPAPs with octahydrospiro[cyclohexan-1,5'-indene]-2,4,6-trione core and complicated PPAPs produced by intramolecular [4 + 2] cycloadditions of MPAPs, are brought into the PPAP family. Some PPAPs' relative or absolute configurations are reassigned or critically discussed, and the confusing trivial names in PPAPs investigations are clarified. Pharmacologic studies have revealed a new molecular mechanism whereby hyperforin and its derivatives regulate neurotransmitter levels by activating TRPC6 as well as the antitumor mechanism of garcinol and its analogues. The antineoplastic potential of some type B PPAPs such as oblongifolin C and guttiferone K has increased significantly. As a result of the recent appearances of innovative synthetic methods and strategies, the total syntheses of 22 natural PPAPs including hyperforin, garcinol, and plukenetione A have been accomplished.

Novel Targets for Stroke Therapy: Special Focus on TRPC Channels and TRPC6

“…By contrast, several studies have indicated that TRPC6 channels could also be store-operated (Yu et al, 2003;El Boustany et al, 2008). Hyperforin has been shown to specifically activate TRPC6 channels, which is mainly responsible for the antidepressant effect of St. John's wort (Yang et al, 2018). There is also a close relation between TRPC6 and reactive oxygen species.…”

Chemical and Biological Aspects of Garcinol and Isogarcinol: Recent Developments

“…[11] Several reviews and book chapters covered the extensive chemistry and biological activities of garcinol and isogarcinol over the last decade. [4,6,7,10,11] The present review highlights the most recent proceedings in this field.…”

“…Their modes of action are diverse and include the inhibition of NF‐ κ B and STAT as well as of histone acetyl transferases (HATs) . Several reviews and book chapters covered the extensive chemistry and biological activities of garcinol and isogarcinol over the last decade . The present review highlights the most recent proceedings in this field.…”

“…In India, for example, plants or plant products from Boswellia , Curcuma , Plumbago , Lawsonia , and Garcinia among others, whose manifold activities were confirmed by modern laboratories meanwhile, have been applied by traditional healers until today . Garcinia species produce the biologically active benzophenones/polycyclic polyprenylated acylphloroglucinols (PPAPs) garcinol and isogarcinol which have raised the interest of chemists and molecular biologists alike ( Figure ) . Garcinol is easily available in large amounts and high purity by extraction of dried kokum plums ( Garcinia indica ) followed by chromatographic purification and/or crystallization .…”

“…[4,5] Garcinia species produce the biologically active benzophenones/polycyclic polyprenylated acylphloroglucinols (PPAPs) garcinol and isogarcinol which have raised the interest of chemists and molecular biologists alike (Figure 1). [6,7] Garcinol is easily available in large amounts and high purity by extraction of dried kokum plums (Garcinia indica) followed by chromatographic purification and/or crystallization. [6,8] Isogarcinol is easily prepared from garcinol by treatment with diluted hydrochloric acid.…”