page_title: Hoiamides
section_title: Hoiamide A
hierarchical_section_title: Hoiamides / Bioactivity / Hoiamide A
caption_attribution_description: English: The structure of Hoiamide A and B
context_page_description: The hoiamides are a class of small molecules recently characterized from isolations of secondary metabolites of cyanobacteria that feature a triheterocyclic system. Hoiamide A and B are cyclic while Hoiamide C and D are linear. Hoiamide A and B demonstrate neurotoxicity by acting on mammalian voltage gated sodium channels, while hoiamide D shows inhibition of the p53/MDM2 complex. The hoiamides are promising therapeutic targets, making their total synthesis an attractive feat.
context_section_description: In mouse neocortical neurons, Hoiamide A acts as a partial agonist to site two of the mammalian voltage gated sodium channel (VGSC).  In electrically excitable cells VGSC allow the influx of sodium that causes the rising phase of the action potential. Hoiamide A stimulated sodium influx with EC50 of 1.7 micromolar in mouse neocortical neurons 
  VGSC have at least six neurotoxic sites that act as targets for small molecules. By using a radioligand probe [3H]BTX  known to bind to neurotoxic site two on the VGSC alpha subunit, a group found that hoiamide A must bind to site two as well, given its inhibition of [3H]BTX.  A full agonist of VGSC site two, batrachotoxin, was then used to determine to what extent hoiamide A acted as an agonist. The experiments demonstrated that hoiamide A is a partial agonist because the maximum sodium influx hoiamide A binding caused was less than that of batrachotoxin. 
  Another study found that hoiamide A stimulated capspase-3 activity, lactic acid dehydrogenase efflux, and nuclear condensation. These processes are specifically and uniquely involved in necrosis and apoptosis, suggesting that hoiamide A is involved neuronal death by both necrosis and apoptosis.
caption: The chemical structure of hoiamide A and B
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