Bioactive Azepine-Indole Alkaloids from Psychotria nemorosa

Abstract

Phytochemical investigation of the alkaloid extract of the aerial parts ofPsychotria nemorosa led to the isolation and characterization of 10 azepine-indole alkaloids, i.e., cimitrypazepine (1), fargesine (2), nemorosines A (3) and B (12), nemorosinosides A-F (4-9), as well as two β-carboline derivatives, 10hydroxyisodolichantoside (10) and 10-hydroxydolichantoside (11), an isoxazole alkaloid, nemorosinoside G (13), serotonin (14), bufotenine (15), and (S)-gentianol ( 16).Compounds 3-13 have not yet been described. These compounds were isolated by semipreparative HPLC and their structures determined by means of HRMS, NMR, and ECD measurements. In addition, the monoamine oxidase-A (MAO-A), MAO-B, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) inhibitory activities were evaluated. Alkaloids 1-3 inhibited the MAO-A activity with IC50 values of 1.4, 1.4, and 0.9 µM, respectively. 3The genus Psychotria, a member of the Rubiaceae family, has been widely studied because of its effects on the central nervous system (CNS). Some species of the genus, like P. viridis, are used to prepare Ayahuasca, a hallucinogenic beverage consumed by Amazon Indian tribes. 1 Recently, this preparation has attracted the attention of researchers due to its pharmacological potential, mainly to treat depression. [1][2][3] Other species have been described to treat dementia, which is corroborated by pharmacological studies. Their capacity to modulate key enzymes related to neurodegeneration, e.g. acetylcholinesterase (AChE), butyrylcholinesterase (BChE), monoamine oxidase A (MAO-A), MAO-B, and catechol-O-methyltransferase (COMT) has been demonstrated. [4][5][6][7][8][9][10][11][12][13] In this sense, Psychotria is considered as an important source of active compounds

Azepine-Indole Alkaloids From Psychotria nemorosa Modulate 5-HT2A Receptors and Prevent in vivo Protein Toxicity in Transgenic Caenorhabditis elegans

“…The alkaloid fraction PNAF was obtained from the leaves of P. nemorosa as previously described (Voucher number FURB41750-Dr. Roberto Miguel Klein Herbarium; SisGen/Brazil code AA26CBC) (Klein-Júnior et al, 2020). For nemorosine A (1), and fargesine (2), isolation and elucidation procedures were described before (Klein-Júnior et al, 2020). Both compounds were dissolved in dimethyl sulfoxide (DMSO) as vehicle and stored at -20 • C until use.…”

“…Stimulated by the research on Ayahuasca, further Psychotria species became the subject of pharmacological and pharmacobotanical studies. Several indole alkaloids have been isolated and evaluated regarding their bioactivity on proteins related to Alzheimer’s disease (AD) and Parkinson’s disease (PD) ( Passos et al, 2013 ; dos Santos Passos et al, 2015 ; Klein-Júnior et al, 2016 , 2017 , 2020 ).…”

Application of HPLC-DAD for In Vitro Investigation of Acetylcholinesterase Inhibition Activity of Selected Isoquinoline Alkaloids from Sanguinaria canadensis Extracts

“…Many plant extracts demonstrate acetylcholinesterase activity, for example, extract from Crinum jagus containing Amaryllidaceae and isoquinolinone alkaloids [6], Cryptocarya species containing isoquinoline alkaloids [10], Narcissus pseudonarcissus L. containing Amarylidaceae alkaloids [7], Catharanthus roseus containing indole alkaloids [9], secophenanthroindolizidine and proaporphine alkaloids from Cryptocarya densiflora Blume [10], Ocotea percoriacea containing benzylisoquinoline, bisbenzylisoquinoline, aporphine, proaporphine, phenanthrene, and morphinane alkaloids [9], Rauvolfia vomitoria containing monoterpene indole alkaloids [11], Crinum jagus containing Amarylidaceae and isoquinoline alkaloids [6], Lycoris longituba containing Amaryllidaceae alkaloid [12], Psychotria leiocarpa containing alkaloid vincosamide [13], Huperzia serrata containing macrocyclic Lycopodium alkaloids [14], Psychotria nemorosa containing azepine-indole alkaloids [15], Uncaria rhynchophylla containing indole alkaloids [16], Berberis vulgaris containing isoquinoline alkaloids [17], Lycopodium platyrhizoma containing Lycopodium alkaloids [18], Huperzia cunninghamioides containing Lycopodium alkaloids [19], Corydalis mucronifera containing isoquinoline alkaloids [20], Palicourea sessilis containing indole alkaloids [21], and Zephyranthes candida containing galanthamine, plicamine, and secoplicamine [22]. There have also been published articles summarizing the application of plant materials containing alkaloids for inhibition of acetylcholinesterase activity [23,24].…”

“…In their method the kinetics of acetylthiocholine iodide hydrolysis by acetylcholinesterase were measured spectrophotometrically. Currently, measurements are most often carried out with the application of 96-well microplates [7,9,12,15,21].…”

Rhodium(II)‐Catalyzed [4+3] Cyclization of Triazoles with Indole Derivatives and Its Application in the Total Synthesis of (±)‐Aurantioclavine

“…This special unit consists of only three rings, but the related natural products exhibited a variety of important biological activities. [ 1a ] For example, fargesine, which was isolated from Evodia fargesii , demonstrated inhibitory activity on monoamine oxidase‐A; [ 1 ] hyrtinadine C, isolated from the marine sponge Hyrtios sp., showed antimicrobial activity. [ 2 ] In addition, communesin F, which has attracted much attention due to significant cytotoxicity and exquisite structural complexity, also contains an azepino[5,4,3‐ cd ]indole core.…”