geoscience.net logo
+ Resolve Article
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter

+ Translate
+ Subscribe to Site Feed
GeoScience Most Shared ContentMost Shared Content

Synthetic polyamines as potential amine oxidase inhibitors: a preliminary study


, : Synthetic polyamines as potential amine oxidase inhibitors: a preliminary study. Amino Acids 42(2-3): 913-928

In the last few decades, medicinal chemists have carried out extensive research on synthetic polyamines for use as anticancer drugs and multitarget-directed ligands in neurodegenerative diseases. The aim of this study was to evaluate the effect of some synthetic polyamines as inhibitors of two new potential targets, human semicarbazide-sensitive amine oxidase/vascular adhesion protein-1 (SSAO/VAP-1) and monoamine oxidases B (MAO B), enzymes involved in various multi-factorial diseases such as Alzheimer s disease. N,N?-Dibenzyl-dodecane-1,12-diamine (Bis-Bza-Diado), a newly synthesised compound, and ELP 12, a muscarinic cholinergic M2 receptor antagonist, were found to behave as reversible and mixed non-competitive inhibitors of both amine oxidases (dissociation constants of about 1 ?M). ELP 12 was found to be more selective for SSAO/VAP-Combining kinetic and structural approaches, the binding mode of ELP 12 to SSAO/VAP-1 was investigated. ELP 12 may bind at the entrance of the active site channel by ionic interactions with ASP446 and/or ASP18; one end of the polyamine may be accommodated inside the channel, reaching the TPQ cofactor area. The binding of ELP 12 induces rearrangement of the secondary structure of the enzyme and impedes substrate entry and/or product release and catalysis. These structural data reveal that the entrance and the first part of the SSAO/VAP-1 channel may be considered as a new target area, or a secondary binding site , for modulators of human SSAO/VAP-1 activity. These results indicate ELP 12 and Bis-Bza-Diado as new skeletons for the development of novel SSAO/VAP-1 and MAO B inhibitors.

US$19.90

PMID: 21858471

DOI: 10.1007/s00726-011-1006-z


Other references

Stull, L.B.; Tuohy, V.; Moravec, C.S., 1999: An autoimmune model of cardiac dysfunction in mice. FASEB Journal 13(4 PART 1): A510, March 12

Sterk, V.; Beslin, R.; Vulic, I., 1976: Protective value of a vaccine against foot-rot in sheep (Clovax). In a trial of the vaccine in 400 sheep, incidence of the condition was reduced, 12 months after the first vaccination, from 20% to 0.6%, and the immunity persisted for at least nine months.

Lu, B.; Liang, Y., 2015: Pagetoid spread of bladder urothelial carcinoma to the vagina and vulva. To study the clinicopathologic features of a rare disease of pagetoid urothelial intraepithelial neoplasia (PUIN) in the vulva. We reviewed a case of PUIN in a Chinese woman with a long history of bladder urothelial carcinoma. The patient presente...

Bhatnagar, D.S.; Sharma, R.C.; Gurnani, M.; Sundaresan, D., 1977: The Karnal Sahiwal and Red Sindhi cows. The Sahiwal herd originated in 1910, whereas the Red Sindhi herd was started in 1953. Selective breeding has been carried out with the purpose of upgrading local cattle. Progeny testing was initiated in 1961. Since Sahiwals are not generally in de...

Elkins, I.J.; McGue, M.; Malone, S.; Iacono, W.G., 2004: The effect of parental alcohol and drug disorders on adolescent personality. Objective: The relationship of parental alcohol or drug diagnosis to offspring personality was examined in a population-based sample of 17-year-old twins (568 girls and 479 boys) participating in the Minnesota Twin Family Study. Whether offspring...

Nakamura, S.; Maeda, K.; Umezawa, H., 1964: The Structure Of Griseolutein B. Journal of Antibiotics 17: 33-36

Anonymous, 1984: Coloured sheep and their products. Papers presented at the World Congress held at Lincoln College and Massey University, New Zealand, 20-31 January, 1984. The papers in this publication are the Proceedings of the Second Congress on Coloured Sheep, the first Congress having been held at Adelaide, Australia, in 1979. They are classified under the following topics: (1) Coloured sheep around the world;...

Castro, G.; Castro, JS., 1988: Dovekie at Island Beach State Park, New Jersey. Cassinia. 1986-1987 ; 61-62 No. 62

Hasenmueller W.A. (leader); Gray H.H. (leader); Carr D.D. (leader), 1979: Organizational day; New Harmony, Indiana. Guidebook Series - Illinois State Geological Survey 15, Part 1): 8

Both, Christiaan, 2002: Fitness costs of polygyny in female pied flycatchers Ficedula hypoleuca. Variance in mating systems can only be understood if the fitness consequences of the available options are known for both sexes. In Pied Fly-catchers Ficedula hypoleuca it has for long been suggested that females pairing with already mated males p...