Bromotyrosine derivative

Psammaplin A (208) Symmetrical bromotyrosine- derived disulfide Panobinostat (LBH-589) (209) Oncology Inhibits histone deacetylase (HDAC) Phase T/IT/ITT Novartis 945,946... 

McCulloch MWB, Coombs GS, Banerjee N, Bugni TS, Cannon KM, Harper MK, Veltri CA, Virshup DM. (2009) Psammaplin A as a general activator of cell-based signaling assays via HDAC inhibition and studies on some bromotyrosine derivatives. Bioorg Med Chem 17 2189-2198. 

There are also some natural products that were identified as inhibitors of DNMTs [87]. Certain disulfide bromotyrosine derivatives, such as psammaplin... 

Similarly, Aplysina sp.(Fig. 10.7), which show a dramatic change in color from yellow to black when exposed to air, contain cytotoxic compounds including bromotyrosine-derivative alkaloids, purealidins (Ishibashi et ah, 1991 Yagi et ah, 1993), aplysamine 2 (Xynas and Capon, 1989), and purpuramin G (Fattorusso et ah, 1970 Fig. 10.8). 

Ishibashi, M., Tsuda, M., Ohizumi, Y., Sasaki, T., and Kobayashi, J. (1991). Purealidin A, a new cytotoxic bromotyrosine-derived alkaloid from the Okinawan marine sponge Psammaplysilla purea. Experientia 47, 299-300. 

Maru, N., Koyama, T., Ohno, O., Yamada, K., and Uemura, D. (2010a). Sunabedine, a novel toxic bromotyrosine-derivative alkaloid from Okinawan sponge, order Verongida. ELeterocycles 82, 371-375. 

Xynas, R. and Capon, R. J. (1989). Two new bromotyrosine-derived metabolites from an Australian marine sponge, Aplysina sp. Aust. ]. Chem. 42,1427-1433. 

Yagi, H., Matsunaga, S., and Fusetani, N. (1993). Purpuramines A-I, new bromotyrosine-derived metabolites from the marine sponge Psammaplysilla purpurea. Tetrahedron 49, 3749-3754. 

Four minor metabolites, psammaplins B-D (503-505) and presammaplin A (506) were isolated from Psammaplysilla purpurea, in addition to psammaplin A (500). Psammaplin B (503) is a thiocyanate bromotyrosine derivative, while psammaplin C (502) is a sulfanamide. Psammaplin D (505) displayed antimicrobial activity and mild tyrosine kinase inhibition [429]. The psammaplins Ai (507) and A2 (508) and aplysinellins A (509) and B (510) were isolated from Aplysinella rhax from both Pohnpei and Palau. These compounds inhibit famesyl protein transferase and leucine aminopeptidase [430]. Another sample of A. rhax from the Great Barrier Reef, Australia contained psammaplin A 11 -sulfate (511) and bisaprasin ll -sulfate (512), both of which inhibited [3H]-l,3-dipropyl-8-cyclopentylxanthine binding to rat brain adenosine Ai receptors [431]. 

Other biologically active bromotyrosine-derived metabolites of marine origin include aeroplysinin, Fig. (48) as cytotoxic and tyrosine kinase inhibitor [382,383], fistularin isolated from Aplysina circheri which exhibited antiviral activity [384], and ceratinamides A and B, antifouling metabolites from Pseudoceratina purpurea [385],... 

Although marine organisms produce a large number of isocyanates, isothiocyanates, and formamides, the corresponding thiocyanates have rarely been encountered. Indeed, the thiocyanate functionality has only been found in six sesquiterpenes (263-268), in four tricyclic quinoline alkaloids (271-274), and in psamaplin B (172) (included in the bromotyrosine derivatives discussed in the disulfide/polysulfide section). They have been found in marine sponges, as well as in nudibranches and tunicates. 

Fusetani N, Masuda Y, Nakao Y, Matsunaga S, van Soest RWM (2001) Three New Bromotyrosine Derivatives Lethal to Crab from the Marine Sponge, Pseudoceratina purpurea. Tetrahedron 57 7507... 

Jang J-H, van Soest RWM, Fusetani N, Matsunaga S (2007) Pseudoceratins A and B, Antifungal Bicyclic Bromotyrosine-Derived Metabolites from the Marine Sponge Pseudoceratina purpurea. J Org Chem 72 1211... 

Bromotyrosine-Derived Metabolites from the Sponge Psammaplysilla purpurea. Chem Pharm Bull 51 990... 

Matsunaga S, Kobayashi H, van Soest RWM, Fusetani N (2005) Novel Bromotyrosine Derivatives That Inhibit Growth of the Fish Pathogenic Bacterium Aeromonas hydrophila, from a Marine Sponge Hexadella sp. J Org Chem 70 1893... 

Takada N, Watanabe R, Suenaga K, Yamada K, Ueda K, Kita M, Uemura D (2001) Zamamistatin, a Significant Antibacterial Bromotyrosine Derivative, from the Okinawan Sponge Pseudoceratina purpurea. Tetrahedron Lett 42 5265... 

Ciminiello P, Dell Aversano C, Fattorusso E, Magno S (2001) Archerine, a Novel Anti-Histaminic Bromotyrosine-Derived Compound from the Caribbean Marine Sponge Aplysina archeri. Eur J Org Chem 55... 

Encamacion RD, Sandoval E, Malmstr0m J, Christophersen C (2000) Calafianin, a Bromotyrosine Derivative from the Marine Sponge Aplysina gerardogreeni. J Nat Prod 63 874... 

Kijjoa A, Watanadilok R, Sonchaeng P, Silva AMS, Eaton G, Herz W (2001) 11,17-Dideoxyagelorin A and B, New Bromotyrosine Derivatives and Analogs from the Marine Sponge Suberea aff. praetensa. Z Naturforsch 56c 1116... 

Ankudey FJ, Kiprof P, Stromquist ER, Chang LC (2008) New Bioactive Bromotyrosine-Derived Alkaloid from a Marine Sponge Aplysinella sp. Planta Med 74 555... 

This sponge contains three high-molecular-weight bromotyrosine derivatives,44 i.e. fistularin-1 (37), fistularin-2 (38), and fistularin-3 (39). 

In a very interesting report from 2001, Ciminiello and coworkers [73] reported the isolation and structural characterization of the complex bromotyrosine-derived imidazole alkaloid archerine (38) that was isolated from the Caribbean marine... 

Compounds obtained from natural sources have always contributed to the development of small molecules for various targets in the history of medicinal chemistry. Recently, several small molecules derived from natural products have been shown to possess Icmt inhibitory activity [72,73]. This effort to discover other natural product inhibitors of Icmt utilized a HTS approach. Of the approximately 6 x 10 extracts screened, the extract from the order Verongida displayed Icmt inhibition. A bromotyrosine-derived chemotaxonomic marker characterizes marine sponges in this order. The extract from Pseudoceratina sp. contained a compound with a bromotyrosyl-spermine-bromotyrosyl sequence, named spermatinamine... 

Bromotyrosine-derived metabolites are often encountered in marine sponges of the families Aplysinidae and Pseudocer-atidae, in particular Pseudoceratina (= Psammaplysilla) purpurea. They show a variety of biological activities, which include antimicrobial, enzyme inhibitory, and antifouling activities. Psammaplysin A (47) is antimicrobial, cytotoxic, and antifouling, whereas psammaplin A (48) is an inhibitor of histone deacetylase (2). The marine sponge lanthella basta synthesizes at least 25 bastadins that are linear or cyclic peptides composed of four bromotyrosine residues [bastadin 5 (49)] and show antimicrobial, cytotoxic, and enzyme inhibitory activities as well as interaction with Ca + channels (21). 

ABSTRACT Marine invertebrates such as ascidians, sponges and others are a prolific source of bioactive secondary metabolites. We have isolated a variety of marine natural products from the Okinawan marine invertebrates by using the sea urchin egg assay. Our recent work, the isolation, structure determination and activities of chlorinated macrolides, sesterterpenic acids, a bromotyrosine derivative, acetogenin derived endoperoxides, diterpene alkaloids, sesquiterpene quinones and spiro-sesquiterpenes, is presented in this article. The syntheses of these metabolites are also described. 

Fractionation of the aqueous MeOH-soluble extract guided by antibacterial activity against Rhodospirillum salexigens, which has adhering properties and forms a microbial biofilm [28], led to the isolation of a novel bromotyrosine derivative, zamamistatin (17) [29]. In its ESIMS spectrum, 17 showed 1 4 6 4 1 quintet ion peaks at m/z 697, 699, 701, 703 and 705, indicative of the presence of four bromine atoms. The molecular formula was determined to be Ci8Hi8Br4N204 by HRESIMS. The observation of only 9 carbons by NMR and the specific rotation of +248° suggested that 17 was an optically active dimmer with a symmetrical structure. Not many resonances in the H and NMR spectra of 17 in contrast to its molecular formula made the structure determination of 17 difficult. 

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