Fifteen bromotyrosine-derived alkaloids were isolated from the sponge Pseudoceratina cf. purpurea. The acetylcholinesterase-inhibiting activity of all the isolated compounds were examined; to purealidin Q, isoanomoian A, aplyzanzine A, and aplysamine 2 were active with IC50 values of 1.2, 70, 104, and 1.3 μM, respectively. On the other hand, antiproliferative activity against MCF-7 cells of aerophobin 1 gave an IC50 value of 0.8 μM. The Michaelis-Menten plots of the active alkaloids indicated that all the four compounds inhibited acetylcholinesterase in a non-competitive manner. The structures of the active compounds suggested that the N, N-dimethylaminopropyloxydibromotyramine moiety may play an important role in the enzyme-inhibiting activity, presumably on the anionic and hydrophobic binding sites.
(a) GrutzendlerJ., MorrisJ.C. (2001) Cholinesterase inhibitors for Alzheimer's disease. Drugs, 61, 41–52;(b) Tõugu V. (2001) Acetylcholinesterase: Mechanism of catalysis and inhibition. Current Medicinal Chemistry – Central Nervous System Agents, 1, 155–170; (c) Singh M, Kaur M, Kukreja H, Chugh R, Silakari O, Singh D. (2013) Acetylcholinesterase inhibitors as Alzheimer therapy: From nerve toxins to neuroprotection. European Journal of Medicinal Chemistry, 70, 165–188; (d) Mullane K, Williams M. (2013) Alzheimer's therapeutics: Continued clinical failures question the validity of the amyloid hypothesis – but what lies beyond? Biochemical Pharmacology, 85, 289–305; (e) Anand R, Gill KD, Mahdi AA. (2014) Therapeutics of Alzheimer's disease: Past, present and future. Neuropharmacology, 76, 27–50.
2.
FattorussoE., MinaleL., SadanoD. (1972) Aeroplysinin 1, an antibacterial bromo-compound from the sponge Verongia aerophoba. Journal of the Chemical Society, Perkin Transaction I, 3, 16–18.
3.
LongeonA., GuyoutG., VaceletJ. (1990) Araplysillins I and II: Biologically active dibromotyrosine derivatives from the sponge Psammaplysilla arabica. Experientia, 46, 548–550.
4.
(a) KobayashiJ., TsudaM., AgemiK., ShigemoriH., IshibashiM., SasakiT., MikamiY. (1991) Purealidins B and C, new bromotyrosine alkaloids from the Okinawan marine sponge Psammaplysilla purea. Tetrahedron, 47, 6617–6622;(b) Kobayashi J, Honma K, Sasaki T, Tsuda M. (1995) Purealidins J-R, new bromotyrosine alkaloids from the Okinawan marine sponge Psammaplysilla purea. Chemical and Pharmaceutical Bulletin, 43, 403–407.
5.
GopichandY., SchmitzF.J. (1979) Marine natural products: Fistularins-1, -2, -3 from the sponge Aplysina fistularis forma fulva. Tetrahedron Letters, 20, 3921–3924.
6.
ManciniI., GuellaG., LabouteP., DebitusC., PietraF. (1993) Hemifistularin 3: A degraded peptide or biogenetic precursor? Isolation from a sponge of the order Verongida from the Coral Sea or generation from base treatment of 11-oxofistularin 3. Journal of the Chemical Society, Perkin Transaction I, 24, 3121–3125.
7.
KottakotaS.K., EvangelopoulosD., AlnimrA., BhaktaS., McHughT.D., GrayM., GroundwaterP.W., MarrsE.C., PerryJ.D., SpillingC.D., HarburnJ.J. (2012) Synthesis and biological evaluation of purpurealidin E-derived marine sponge metabolites: Aplysamine 2, aplyzanzine A, and suberedamines A and B. Journal of Natural Products, 75, 1090–1101.
8.
EvansT., RudiA., IlanM., KashmanY. (2001) Aplyzanzine A, a new dibromotyrosine derivative from a Verongida sponge. Journal of Natural Products, 64, 226–227.
9.
XynasR., CaponR.J. (1989) Two new bromotyrosine-derived metabolites from an Australian marine sponge Aplysina sp. Australian Journal of Chemistry, 42, 1427–1433.
10.
CiminoG., De RossaS., De StefanoS., SelfR., SodanoaG. (1983) The bromo-compounds of the true sponge Verongia aerophoba. Tetrahedron Letters, 24, 3029–3032.
11.
(a) EllmanG.L., CourtneyK.D., AndresV.Jr., FeatherstoneR.M. (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochemical Pharmacology, 7, 88–95; (b) Ingkaninan K, Temkitthaworn P, Yuyaem T, Thongnoi W. (2003) Screening for acetylcholinesterase inhibitory activity in plants used in Thai traditional rejuvenating remedies, Journal of Ethnopharmacology, 89, 261–264.
12.
SkehanP., StorengR., ScudieroD., MonksA., McMahonJ., VisticaD., WarrenJ.T., BokeschH., KenneyS., BoydM.R. (1990) New colorimetric cytotoxicity assay for anticancer drug screening. Journal of the National Cancer Institute, 82, 1107–1112.
13.
BellutiF., Bartolini, BottegoniG., BisiA., CavalliA., AndrisanoV., RampaA. (2011) Benzophenone-based derivatives: A novel series of potent and selective dual inhibitors of acetylcholinesterase and acetylcholinesterase-induced beta-amyloid aggregation. European Journal of Medicinal Chemistry, 46, 1682–1693.
