72479-07-3Relevant academic research and scientific papers
In vitro structure-activity relationships of aplysinopsin analogs and their in vivo evaluation in the chick anxiety-depression model
Lewellyn, Kevin,Bialonska, Dobroslawa,Loria, Melissa J.,White, Stephen W.,Sufka, Kenneth J.,Zjawiony, Jordan K.
, p. 7083 - 7090 (2013/11/06)
Aplysinopsins are tryptophan-derived natural products that have been isolated from a variety of marine organisms and have been shown to possess a range of biological activities. In vitro receptor binding assays showed that of the 12 serotonin receptor subtypes, analogues showed a high affinity for the 5-HT2B and 5-HT2C receptor subtypes, with selectivity for 5-HT2B over 5-HT2C. While no conclusions could be drawn about the number and position of N-methylations, bromination at C-4 and C-5 of the indole ring resulted in greater binding affinities, with Ki's as low as 35 nM. This data, combined with previous knowledge of the CNS activity of aplysinopsin analogs, suggested that these compounds may have potential as leads for antidepressant drugs. Compounds 3c, 3u, and 3x were evaluated in the chick anxiety-depression model to assess their in vivo efficacy. Compound 3c showed a modest antidepressant effect at a dose of 30 nM/kg in the animal model.
Synthesis and evaluation of aplysinopsin analogs as inhibitors of human monoamine oxidase A and B
Lewellyn, Kevin,Bialonska, Dobroslawa,Chaurasiya, Narayan D.,Tekwani, Babu L.,Zjawiony, Jordan K.
experimental part, p. 4926 - 4929 (2012/08/28)
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. Three compounds displayed significant MAO inhibitory activity and selectivity. The compound (E)-5-[(6-bromo-1H-indol-3-yl)methylene]-2-imino-1,3- dimethylimidazolidin-4-one (3x) possessed an IC50 of 5.6 nM at MAO-A and had a selectivity index of 80.24. An SAR study revealed that multiple N-methylations, one of which should be at position N-2′, and bromination at C-5 or C-6 are important factors for MAO-A potency and selectivity.
A new synthesis of 5-bromoaplysinopsin, 6-bromoaplysinopsin and 3'-demethylaplysinopsin and their biological activities
Gulati, Deepa,Chauhan, P. M. S.,Pratap, Ram,Bhakuni, D. S.
, p. 10 - 16 (2007/10/02)
A new synthesis of 5-bromoaplysinopsin (11), 6-bromoaplysinopsin (15) and 3'-demethylaplysinopsin (24) has been developed.A number of their analogues have been synthesized and evaluated for biological activities.Of the compounds tested, compounds 5, 7-9 a
Aplysinopsin-Type Alcaloids from Dendrophyllia sp., a Scleractinian Coral of the Family Dendrophylliidae of the Philippines. Facile Photochemical (Z/E) Photoisomerization and Thermal Reversal
Guella, Graziano,Mancini, Ines,Zibrowius, Helmut,Pietra, Francesco
, p. 1444 - 1450 (2007/10/02)
The dendrophylliid Dendrophyllia sp. of Palawan contains the indole alkaloids 2'-demethylaplysinopsin (4) and 2'-demethyl-3'-N-methylaplysinopsin (6) and their 6-bromo analogues in a (Z/E) ratio larger than 95 : 5; these mixtures undergo facile photoisomerization to give mixtures richer in the (E) stereoisomer which undergo thermal isomerization to give back the original mixtures.
