Chemistry: molecular biology and microbiology – Micro-organism – tissue cell culture or enzyme using process... – Preparing compound containing saccharide radical
Patent
1997-06-30
1999-02-02
Witz, Jean C.
Chemistry: molecular biology and microbiology
Micro-organism, tissue cell culture or enzyme using process...
Preparing compound containing saccharide radical
435184, 4352535, 514 42, C12P 1928, C12N 999, C12N 120, A01N 4304
Patent
active
058663770
DESCRIPTION:
BRIEF SUMMARY
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to novel aminooligosaccharide derivative and pharmaceutically acceptable non-toxic salts thereof, which possess potent saccharide hydrolase inhibition and antibacterial activities. The invention also relates to a process for preparing the same and to pharmaceutical compositions containing the same as active ingredients.
2. Description of the Prior Art
It has been well known that inhibitors of saccharide hydrolases such as amylase and saccharase may be applied in the treatment or prevention of diabetes, hyperlipoproteinemia, hyporlipidemia, obesity or other secondary symptoms caused thereby.
In this regard, several aminooligosaccharide derivatives, for example, A-2396 which is produced by Streptomyces sp. A2396(see: Japanese Patent Laid-Open (Sho)54-92909), Oligostatin which is provided by Streptomyces myxogenes(see: J. Antibiotics, 34:1424-1433 (1981)), Adiposin (see: J. Antibiotics, 35:1234-1236(1982)) and NS complex which is produced by Streptomyces flavochromogenes(see: Japanese Patent Laid-Open (Hei)3-19239), have been reported as potent inhibitors of the saccharide hydrolases.
On the other hand, the NS complex, whose chemical structure is quite similar to the aminooligosaccharide derivative of the invention, is represented by the formula below: ##STR1##
In accordance with the present invention, the inventors isolated novel aminooligosaccharide derivative from a soil microorganism categorized as Streptomyces sp., and discovered that it can be applied as potent inhibitors for saccharide hydrolases and antibacterial agents as well.
SUMMARY OF THE INVENTION
The primary object of the present invention is, therefore, to provide novel aminooligosaccharide derivative, CK-4416 represented by the general formula(I) and salts thereof: ##STR2## wherein: m is an integer of 0 or 1;
The other object of the invention is to provide the use of aminooligosaccharide derivative as inhibitors of saccharide hydrolases and antibacterial agents.
Another object of the invention is to provide a process for preparing aminooligosaccharide derivative from Streptomyces sp. CK-1416.
BRIEF DESCRIPTION OF THE DRAWINGS
The above and the other objects and features of the present invention will become apparent from the following descriptions given in conjunction with the accompanying drawings, in which:
FIG. 1 is a IR spectrum of CK-4416 material of the invention;
FIG. 2 is a .sup.1 H-NMR spectrum of CK-4416;
FIG. 3 is a .sup.13 C-NMR spectrum of CK-4416; and,
FIG. 4 is a FAB-MS/MS spectrum of CK-4416.
DETAILED DESCRIPTION OF THE INVENTION
The present inventors have screened soil microorganisms to isolate a microbe producing the aminooligosaccharide derivative of the invention. The microbe thus isolated was identified as a species of Streptomyces genus and named as Streptomyces sp. CK-4416. In addition, the aminooligo-saccharide derivative produced therefrom are determined to be novel one and named as CK-4416.
CK-4416 is produced from Streptomyces sp. CK-4416 culturing on a medium containing carbon and nitrogen sources under an aerobic condition employing shaking culture or aerobic spinner culture. As a carbon source, commercially available glucose, glycerin, maltose, starch, sucrose, molasses and dextrin may be utilized; as a nitrogen source, commercially available soybean flour, corn steep liquor, beef extract, cotton seed flour, peptone, wheat germ, fish meal, inorganic ammonium salts and NaNO.sub.3, may be utilized; and, CaCO.sub.3, NaCl, KCl, MgSO.sub.4 and phosphate salts may be utilized as inorganic salts. The medium for culturing Streptomyces sp. CK-4416 may further comprise some metal ions such as Fe, Mn and Zn in a trace amount, and antifoaming agent such as plant oils, higher alcohols including octadecanol and silicone compounds, if they are necessary. The medium may also comprise any compound which eases the culture of Streptomyces sp. CK-4416 to produce CK-4416 material with a high yield.
Streptomyces sp. ClK-4416 is cultured in acc
REFERENCES:
patent: 4990500 (1991-02-01), Vertesy et al.
Truscheit et al. "Chemistry and Biochemistry of Microbial alpha-Glucosidase Inhibitors," Angew. Chem. Int. Ed. Engl. (1981) 20: 744-761, 1981.
Carey et al. "Advanced Organic Chemistry. Part B: Reactions and Synthesis," 2nd edition (Plenum Press: New York) (1980) pp. 494-498, 1980.
Shinjuro Namiki, et al., Studies on the .alpha.-Glucoside Hydrolase Inhibitor, Adiposin, I. Isolation and Physicochemical Properties, The Journal of Antibiotics, 35:1234-1236 (1982).
Shinjuro Namiki, et al., Studies on the .alpha.-Glucoside Hydrolase Inhibitor, Adiposin, II. Taxonomic Studies on the Producing Microorganism, The Journal of Antibiotics, 35:1156-1173 (1982).
Jiro Itoh, et al., Oligostatins, New Antibiotics with Amylase Inhibitory Activity, I. Production, Isolation and Characterization, The Journal of Antibiotics, 34:1424-1428 (1981).
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Kunio Kangouri, et al., Studies on the .alpha.-Glucoside Hydrolase Inhibitor, Adiposin, III. .alpha.-Glucoside Hydrolase Inhibitory Activity and Antibacterical Activity in Vitro, The Journal of Antibiotics, 35:1160-1166 (1982).
Shinjuro Namiki, et al., Studies on the .alpha.-Glucoside Hydrolase Inhibitor, Adiposin, IV. Effect of Adiposin on Intestinal Digestion of Carbohydrates in Experimental Animals, The Journal of Antibiotics, 35:1167-1173 (1982).
H.S. Chun and J.W. Kim, a Novel .alpha.-Glucosidase Inhibitor, CKD-711, Proceedings of Seoul Conference on Actinomycetes '97, Research Center for Molecular Microbiology, Seoul National University and Korean Research Group for Actinomycetes, Seoul, Korea, May 23, pp. 23-34 (1997).
D.H. Choung, et al., Determination of the Structure of CK-4416, .alpha.-Glucosidase Inhibitors, using Nuclear Magnetic Resonance, Scientific Meeting and General Assembly Commemorating 30th Anniversary, The Biochemical Society of Republic of Korea, Seoul, Korea, May 2-3, p. 83 (1997).
Chang Hung Bae
Chun Hyoung Sik
Kim Jong Gwan
Kim Jung Woo
Kim Sun Ho
Chong Kun Dang Corporation
Hanley Susan
Witz Jean C.
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