Isopimaric acid is a diterpenoid resin acid that has been found in P. nigra and has diverse biological activities.1,2,3,4 It is active against clinical isolates of epidemic methicillin-resistant S. aureus (EMRSA; MICs = 32-64 µg/ml).1 Isopimaric 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).2 It opens large conductance calcium-activated potassium channels (BKCa1.1/KCa1.1) in HEK293 cells expressing recombinant channels and the activating β1 regulatory subunit when used at a concentration of 10 µM.3 Isopimaric 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.4 It 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)