Griseolic acid A
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| Category | Enzyme inhibitors |
| Catalog number | BBF-01285 |
| CAS | 79030-08-3 |
| Molecular Weight | 379.28 |
| Molecular Formula | C14H13N5O8 |
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Description
It is produced by the strain of Streptomyces griseoaurantiacus SANK43894. It has the activity of inhibiting cyclic adenosine monophosphate (cAMP) phosphodiesterase [EC 3.1.4.17] with IC50 0.16 X 10-6 mol/L (Extracted from rat brain). Griseolic acid A can stimulate the flow of glycogen and increase the blood sugar level in mice.
Specification
| Synonyms | griseolic acid; 1-(6-Amino-9H-purin-9-yl)-3,6-anhydro-6-C-carboxy-1,5-dideoxy-α-L-talo-4-octenofuranuronic acid |
| IUPAC Name | (2R,3R,3aS,5S)-2-(6-aminopurin-9-yl)-5-[(R)-carboxy(hydroxy)methyl]-3-hydroxy-3,3a-dihydro-2H-furo[3,2-b]furan-5-carboxylic acid |
| Canonical SMILES | C1=C2C(C(C(O2)N3C=NC4=C(N=CN=C43)N)O)OC1(C(C(=O)O)O)C(=O)O |
| InChI | InChI=1S/C14H13N5O8/c15-9-5-10(17-2-16-9)19(3-18-5)11-6(20)7-4(26-11)1-14(27-7,13(24)25)8(21)12(22)23/h1-3,6-8,11,20-21H,(H,22,23)(H,24,25)(H2,15,16,17)/t6-,7-,8+,11-,14+/m1/s1 |
| InChI Key | IAPZXUKYTCQQFE-CVUHLFANSA-N |
Properties
| Appearance | White Powder |
| Boiling Point | 953.3 °C at 760 mmHg |
| Melting Point | >220 °C |
| Density | 2.26 g/cm3 |
| Solubility | Soluble in Water, DMSO |
Reference Reading
1. Biosynthesis of griseolic acids: incorporation of 13C-labeled compounds into griseolic acid A
S Miyakoshi, H Haruyama, T Shioiri, S Takahashi, A Torikata, M Yamazaki J Antibiot (Tokyo). 1992 Mar;45(3):394-9. doi: 10.7164/antibiotics.45.394.
Biosynthesis of griseolic acids, competitive inhibitors of cyclic nucleotide phosphodiesterase, was investigated with the culture of a producing strain of Streptomyces griseoaurantiacus. 13C-Labeled and 15N-labeled compounds were added into the culture, and 13C-enriched and 15N-enriched griseolic acid A was isolated from the culture medium and analyzed by 13C NMR and 15N NMR spectroscopy. The compounds added to growth medium were [2-13C]acetate, [1,2-13C]acetate, [1,4-13C]succinate, [1-13C]glucose, [6-13C]glucose, [2-13C]ribose, and [1-13C, 15N]glycine. The results suggest that adenosine, which is formed from amino acids and sugars contributes the adenine and ribose moieties to griseolic acid A. The data also suggest that a dicarboxylic acid from the Krebs tricarboxylic acid cycle contributes to the dicarboxylic part of the compound.
2. Properties of base-substituted and carboxyl-esterified analogues of griseolic acid, a potent cAMP phosphodiesterase inhibitor
T Yasumoto, Y Iijima, M Kaneko, M Yamazaki Biochem Pharmacol. 1992 May 28;43(10):2073-81. doi: 10.1016/0006-2952(92)90164-e.
Griseolic acid (GA) is a potent cyclic AMP (cAMP) phosphodiesterase (PDE) inhibitor that has an adenine base and two carboxyl groups in its molecule (Nakagawa F, Okazaki T, Naito A, Iijima Y and Yamazaki M, J Antibiot 38: 823-829, 1985). GA analogues were synthesized in which the adenine group was substituted with guanine (6-deamino-2-amino-6-hydroxygriseolic acid, G-GA) or hypoxanthine (6-deamino-6-hydroxygriseolic acid, H-GA). Their inhibitory activities to cyclic GMP (cGMP) PDE and cAMP PDE were compared with GA. For cGMP PDE from rod outer segments of bovine retina, the IC50 values of GA, G-GA and H-GA were 18, 0.040 and 0.12 microM, respectively, with 0.25 microM cGMP as substrate. For type IV PDE isozyme from mouse 3T3 fibroblast cells, the IC50 values of GA, G-GA and H-GA were 0.021, 15 and 11 microM, respectively, with 0.25 microM cAMP as substrate. Thus, GA and G-GA were found to be base-selective inhibitors of type IV PDE of 3T3 cells and type V PDE of bovine retinas, respectively. Esters of carboxylic acids of GA were synthesized in order to increase permeability into cells, and their efficacy was tested by measuring the accumulation of cAMP in 3T3 cells. The dipivaloyloxymethyl ester of GA was found to increase cAMP levels at 0.1 microM, while GA and 3-isobutyl-1-methylxanthine were active only above 100 microM, and the dimethyl ester of GA was inactive. The dipivaloyloxymethyl ester of GA seems to exert its activity after conversion to GA in the cell, since the pivaloyloxymethyl ester was easily hydrolysed by the enzyme action and the dipivaloyloxymethyl ester of GA itself was much less potent an inhibitor of PDE. The dipivaloyloxymethyl ester of GA inhibited thrombin-induced aggregation of platelets and stimulated lipolysis of adipocytes at low concentrations.
3. A cyclic AMP phosphodiesterase inhibitor, 8'-pivaloyloxymethyl ester (POM-ester) of griseolic acid, lowers rabbit intraocular pressure
H K Mishima, Y Kiuchi, T Yokoyama, T Yasumoto, M Yamazaki Curr Eye Res. 1991 Sep;10(9):817-22. doi: 10.3109/02713689109013877.
The effects of griseolic acid (GA), a cyclic-AMP phosphodiesterase (PDE) inhibitor, and its 8'-pivaloyloxymethyl (POM) ester on intraocular pressure (IOP) in rabbits were investigated. When 50 microliters of 1 and 2% GA POM ester solutions were topically applied to one eye in normal rabbits, significant IOP decreases were detected at 2 hrs and at 1 to 5 hrs, respectively. Other than ocular hypotension, no other ocular effects were detected locally even after administration of 2% GA POM ester. A more marked reduction in IOP occurred after the intravitreal injection of the GA POM ester. IOP was also reduced when GA was used in an intravitreal injection but not when it was topically applied. The difference in permeability between GA and GA POM ester across the corneal epithelium may explain why GA failed to reduced IOP following topical administration. GA and the GA POM ester inhibited cAMP PDE in rabbit ciliary body at low concentrations, the I50 being 0.075 microM and 2.4 microM, respectively, with 0.25 microM cAMP as substrate. GA and the GA POM ester markedly increased cAMP levels in vitro in iris-ciliary body specimens. Possibly, GA POM ester or its analogues may represent a new mechanistic class of ocular hypotensive agents.
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
