Chitinase inhibitors

Overall, these chitinase inhibitors provide an interesting example of peptide-carbohydrate mimicry. As described above for several other systems, mimicry consists of a mixture of structurally mimetic interactions and other favorable interactions with the receptor. Of the structurally mimetic interactions, the mimicry by argifin of the N-acetyl group, and part of the pyranosyl... 

Houston DR, Synstad B, Eijsink VGH, Stark MJR, Eggleston IM, van Aalten DMF (2004) Structure-based exploration of cyclic dipeptide chitinase inhibitors. J Med Chem 47(23) 5713-5720... 

Since the isolation of the chitinase inhibitor allosamidin from Streptomyces [90], the aminohydroxy-substituted cyclopentanes have been recognized as powerful and specific inhibitors of glycosidases [91]. The synthesis of (+) [92], as well as of racemic [93] mannostatin, which is a strong mannosidase inhibitor, should be mentioned here (Fig. 1). 

Styloguanidins, e.g. 135, chitinase inhibitors from the marine sponge Stylotella aurantium, inhibit the moulting of cyprid larvae of barnacles at a concentration of 10 ppm [108]. They are closely related to palauamine (67). 

Kato T, Shizuri Y, Izumida H, Yokoyama A, Endo M (1995) Styloguanidines, New Chitinase Inhibitors from the Marine Sponge Stylotella aurantium. Tetrahedron Lett 36 2133... 

Tabudravu JN, Eijsink VGH, Gooday GW, Jaspars M, Komander D, Legg M, Synstad B, van Aalten DMF (2002) Psammaplin A, a Chitinase Inhibitor Isolated from the Fijian Marine Sponge Aplysinella rhax. Bioorg Med Chem 10 1123... 

In 1986 the novel chitinase inhibitor (—)-allosamidin was discovered in fermentation broths of Streptomyces sp. 1713 by Sakuda and coworkers.1 (—)-Allosamidin is unusual inasmuch as it contains two N-acetyl-D-allosamine residues glycosidically linked P-1,4 to one another. In turn, this disaccharide is connected to a cyclopentanoid known as (—)-allosamizoline in the manner shown in Figure 11.1. 

The remarkable hexacyclic alkaloid palau-amine (10) from Stylotella agminata was reported in 1993 (Scheme 3) [8]. Its high immuno-suppresive activity - whilst being reasonably nontoxic - has provoked preclinical studies [8c]. Interestingly, the isomer styloguanidine (11) is a powerful chitinase inhibitor [8b]. 

Nakata, M, Akazawa, S, Kitamura, S, Tatsuta, K, Enantiospecific total synthesis of (—)allosazoline, an aminocyclitol moiety of the insect chitinase inhibitor allosamidin. Tetrahedron Lett., 32, 5363-5366, 1991. 

Allosamidin (2) and its congeners demethylallosamidin (3), methylallosamidin (4), methyl A-demethylallosamidin (5), glucoallosamidin A (6) and glucoallosamidin B (7) are the first examples of endochitinase inhibitors. They were isolated from the mycelial extract of Streptomyces sp. 1713 and related actinomycete SA-684 and A82516. They exhibit the inhibitory activity against the chitinases of the silkworm Bombyx mori in vitro and prevent its larval ecdysis in It has been thought that the chitinase inhibitor would... 

Omura, S., Arai, N., Yamaguchi, Y. eta/. (2000) Argifin, a new chitinase inhibitor, produced by Gliocladium sp. FTD-0668.1. Taxonomy, fermentation, and biological activities. The Journal of... 

Dixon, M.J., Andersen, O.A., van Aalten, D.M. and Eggleston, I.M. (2005) An efficient synthesis of argifin a natural product chitinase inhibitor with chemotherapeutic potential. Bioorganic Medicinal Chemistry Letters, 15, 4717 721. 

The chitinase inhibitor allosamidine is a trisaccharide analogue with two N-acetylallosamine units bonded to a highly functionalized cyclopentano-oxazoline unit - allosamizoline. Analogues have now been described with one JV-acetylallo-samine unit, with the disaccharide bonded to an alternative hydroxyl of the cyclopentane, and thirdly with the oxazoline ring inverted. ... 

Enzyme Inhibition - 2-Acetamido-2-deoxy-D-glucopyranose, chitobiose and chitotriose were P-glycosidically linked to various exo-glycosidase inhibitors, and evaluated as chitinase inhibitors. Good inhibition was found for an JV-formyl-pyrrolidine analogue (transition state mimic) and epoxybutyl chitobioside (an irreversible inhibitor). ... 

Synthesis and activities of aUosamidin and its analogues as chitinase inhibitors 12MRM665. 

Allosamidin, one of the typical secondary metabolites, is isolated from streptomyces using chitinase inhibitors. It can promote the production of chitinase detected in the culture by filtrate, and chitin hydrolytic activity was inhibited by allosamidin. These results suggest that allosamidin acts as a key signal molecule for chitinase production, which may be useful for its growth in the chitin-rich... 

Suzuki, S., Nakanishi, E., Ohira, T., Kawachi, R., Nagasawa, H., and Sakuda, S. 2006. Chitinase inhibitor allosamidin is a signal molecule for chitinase production in its producing streptomyces I. Analysis of the chitinase whose producing is promoted by allosamidin and growth accelerating activity of allosamidin. J. Antibiot (Tokyo), 59 402-409. 

Alkaloid from the marine sponge Stylotella aurantium. Potent chitinase inhibitor. 

Bromo [162339-62-0]. 3-Bromostyloguanidine Ci HjiBrClN O M 498.769 From S. aurantium. Potent chitinase inhibitor. 

Sakuda S, Isogai A, Matsumoio S, Suzuki A. Search for microbial insect growth regularors. 11. Altosamidin, a novel insect chitinase inhibitor. J Antibiot 1987 40 296-300. 

Zhou Z Y, Sakuda S, Yamada Y. Biosynthetic studies on the chitinase inhibitor, allosamidin. Origin of the carbon and nitrogen atoms. J Chem Soc Perkin Trans 1 1992 1992 649-1652. Asano N, Katayama K, Takeuchi M, Fummoto T. Kameda Y, Matsui K. Preparation of 3 amino 3 deoxy derivatives of trehalose and sucrose and thcii activities. ] Antibiot 1989 42 585-590. 

C25H42N4O14 622.625 Aminoglycoside antibiotic. Prod, by Streptomyces sp. Chitinase inhibitor. Insecticide. Powder. [a]o -24.8 (c, 0.5 in O.IM AcOH). 

C24H40N4O14 608.598 Prod, by Streptomyces spp. AT9463 and SA-684. Chitinase inhibitor, insecticide... 

C26H44N4O14 636.652 From Streptomyces sp. Insect chitinase inhibitor. Powder. 

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