Isopimaric acid is a diterpenoid resin acid that has been found inP. nigraand has diverse biological activities.^1,2,3,4It is active against clinical isolates of epidemic methicillin-resistantS. aureus(EMRSA; MICs = 32-64 µg/ml).¹Isopimaric acid is an agonist of retinoid X receptor alpha (RXRα), RXRβ, and RXRγ in a reporter assay using HEK293T cells expressing human receptors (EC₅₀s = 26, 32, and 33 µM, respectively).²It opens large conductance calcium-activated potassium channels (BKCa1.1/K_Ca1.1) in HEK293 cells expressing recombinant channels and the activating β1 regulatory subunit when used at a concentration of 10 µM.³Isopimaric acid potentiates reductions in field excitatory postsynaptic potential (fEPSP) slopes in hippocampal slices and decreases escape latency in the Morris water maze in a 3xTg mouse model of Alzheimer’s disease.⁴It has been found as an environmental contaminant in pulp and paper mill effluent.⁵

1.Smith, E., Williamson, E., Zloh, M., et al.Isopimaric acid from Pinus nigra shows activity against multidrug-resistant and EMRSA strains of Staphylococcus aureusPhytother. Res.19(6)538-542(2005) 2.Merk, D., Grisoni, F., Friedrich, L., et al.Computer-assisted discovery of retinoid X receptor modulating natural products and isofunctional mimeticsJ. Med. Chem.61(12)5442-5447(2018) 3.Imaizumi, Y., Sakamoto, K., Yamada, A., et al.Molecular basis of pimarane compounds as novel activators of large-conductance Ca2+-activated K+ channel α-subunitMol. Pharmacol.62(4)836-846(2002) 4.Wang, L., Kang, H., Li, Y., et al.Cognitive recovery by chronic activation of the large-conductance calcium-activated potassium channel in a mouse model of Alzheimer’s diseaseNeuropharmacology928-15(2015) 5.van den Heuvel, M.R., Ellis, R.J., Tremblay, L.A., et al.Exposure of reproductively maturing rainbow trout to a New Zealand pulp and paper mill effluentEcotoxicol. Environ. Saf.51(1)65-75(2002)