63153-56-0Relevant articles and documents
Identification of aplysinopsin as a blood-brain barrier permeable scaffold for anti-cholinesterase and anti-BACE-1 activity
Nuthakki, Vijay K.,Yadav Bheemanaboina, Rammohan R.,Bharate, Sandip B.
, (2021)
Aplysinopsins are a group of marine-derived indole alkaloids that display diverse array of pharmacological effects. However, their effect on anti-Alzheimer targets has not been reported. Herein, we report the synthesis of aplysinopsin (1) and its effect on cholinesterases and beta-site amyloid-precursor protein cleaving enzyme 1 (BACE-1). It inhibits electric eel acetylcholinesterase (AChE), equine serum butyrylcholinesterase (BChE), and human BACE-1 with IC50 values of 33.9, 30.3, and 33.7 μM, respectively, and excellent BBB permeability (Pe 8.92 × 10?6 cm/s). To optimize its sub-micromolar activity, the first-generation analogs were prepared and screened. Two most active analogs 5b and (Z)-8g were found to effectively permeate the BBB (Pe > 5 × 10?6 cm/s). The N-sulphonamide derivative 5b display better cholinesterase inhibition, whereas the other analog (Z)-8g strongly inhibits BACE-1 (IC50 0.78 μM) activity. The analog 5b interacts primarily with PAS of AChE, and thus exhibit a mixed-type of inhibition. In addition, aplysinopsin along with new analogs inhibited the self-induced Aβ1-42 aggregation. The data presented herein indicate that the aplysinopsin-scaffold holds a potential for further investigation as a multi-targeted anti-Alzheimer agent.
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 aplysinopsin, a marine alkaloid and its analogues and their biological activities
Gulati, Deepa,Chauhan, P. M. S.,Pratap, Ram,Bhakuni, D. S.
, p. 4 - 9 (2007/10/02)
Aplysinopsin (1) and its analogues (3a-3d, 6a-6e and 7d) have been synthesised and evaluated for their broad biological activities.Of the compounds tested, compound 3a, 4b, 5b and 7a show high order of in vitro antileishmanial activity.Compound 3a also shows moderate antiviral activity against Ranikhet disease virus (RDV) and compounds 4d, 4e, 5a, 5b, 6c, and 7d show moderate antimicrobial activity.
