Planta Med 2012; 78 - CL22
DOI: 10.1055/s-0032-1320257

In vitro and in vivo evaluation of the antidepressant activity of aplysinopsin analogs

K Lewellyn 1, D Bialonska 1, 3, ND Chaurasiya 4, BL Tekwani 4, 5, MJ Loria 6, SW White 6, KJ Sufka 2, 5, 6, JK Zjawiony 1, 2
  • 1Department of Pharmacognosy
  • 2Research Institute of Pharmaceutical Sciences, School of Pharmacy, University of Mississippi, University, MS 38677, USA
  • 3Institute of Environmental Sciences, Jagiellonian University, 30–387, Krakow, Poland
  • 4National Center for Natural Products Research, University of Mississippi, University, MS 38677, USA
  • 5Department of Pharmacology, School of Pharmacy, University of Mississippi, University, MS 38677, USA
  • 6Department of Psychology, University of Mississippi, University, MS 38677, USA

Aplysinopsins are tryptophan-derived natural products that have been isolated from a variety of marine organisms. Previous studies have shown aplysinopsin analogs to possess a variety of biological activities, including modulation of neurotransmissions. A series of fifty aplysinopsin analogs was synthesized and assayed for monoamine oxidase A and B inhibitory activity. Several compounds displayed significant MAOI activity and selectivity. Compound 3x possessed an IC50 of 5.6 nM at MAO-A and had a selectivity index of 80.24. This data, combined with previous knowledge of aplysinopsin analogs' CNS activity, suggested that these compounds may have potential as leads for antidepressant drugs. Considering this, three compounds were evaluated in a chick anxiety-depression model to evaluate their in vivo efficacy. Compound 3c showed an antidepressant effect at a dose of 0.03µM/kg in the animal model.