Ribostamycin sulfate (Landamycine, Ribomycine; Ribostamin) is a naturally occuring aminoglycoside-aminocyclitol antibiotic with a broad-spectrum antibiotic activity against various gram-positive and gram-negative bacteria. It is extracted from Streptomyces ribosifidicus. Aminoglycoside class of antibiotics consist of amino groups linked to glycosides, they act by inhibiting protein synthesis via binding to the 30s ribosomal subunit, which results in misreading of the mRNA sequence and inhibition of translocation.
Physicochemical Properties
| Molecular Formula | C17H36N4O14S |
| Molecular Weight | 552.549 |
| Exact Mass | 552.194 |
| Elemental Analysis | C, 36.95; H, 6.57; N, 10.14; O, 40.54; S, 5.80 |
| CAS # | 53797-35-6 |
| Related CAS # | 25546-65-0;53797-35-6 (sulfate); |
| PubChem CID | 20056828 |
| Appearance | White to off-white solid powder |
| Density | 1.6g/cm3 |
| Boiling Point | 907.6ºC at 760 mmHg |
| Melting Point | 175-180ºC |
| Flash Point | 502.7ºC |
| Hydrogen Bond Donor Count | 12 |
| Hydrogen Bond Acceptor Count | 18 |
| Rotatable Bond Count | 6 |
| Heavy Atom Count | 36 |
| Complexity | 674 |
| Defined Atom Stereocenter Count | 13 |
| SMILES | S(=O)(=O)(O[H])O[H].O([C@]1([H])[C@@]([H])([C@]([H])([C@@]([H])([C@@]([H])(C([H])([H])N([H])[H])O1)O[H])O[H])N([H])[H])[C@]1([H])[C@]([H])(C([H])([H])[C@]([H])(C([H])([C@@]1([H])O[C@@]1([H])[C@@]([H])([C@@]([H])([C@@]([H])(C([H])([H])O[H])O1)O[H])O[H])O[H])N([H])[H])N([H])[H] |
| InChi Key | RTCDDYYZMGGHOE-YMSVYGIHSA-N |
| InChi Code | InChI=1S/C17H34N4O10.H2O4S/c18-2-6-10(24)12(26)8(21)16(28-6)30-14-5(20)1-4(19)9(23)15(14)31-17-13(27)11(25)7(3-22)29-17;1-5(2,3)4/h4-17,22-27H,1-3,18-21H2;(H2,1,2,3,4)/t4-,5+,6-,7-,8-,9+,10-,11-,12-,13-,14-,15-,16-,17+;/m1./s1 |
| Chemical Name | (2R,3S,4R,5R,6R)-5-amino-2-(aminomethyl)-6-[(1R,2R,4R,6S)-4,6-diamino-2-[(2S,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]oxy-3-hydroxycyclohexyl]oxyoxane-3,4-diol;sulfuric acid |
| Synonyms | Ribomycine; Ribostamin; SF 733 antibioic sulfate;Landamycine, Riboflavine sulfate; Ribostamycin sulfate; 53797-35-6; Landamycine; Ribomycine; Vistamycin Sulfate; Ribostamin; Ribostamycin (sulfate); SF 733 antibioic sulfate; |
| HS Tariff Code | 2934.99.9001 |
| Storage |
Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition | Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs) |
Biological Activity
| Targets | Bacterial protein synthesis; 30S and 50S ribosomal subunit |
| ln Vitro |
In the biosynthesis of neomycin, ribostamycin serves as an intermediary [1]. Protein disulfide isomerase (PDI) chaperone activity was inhibited by ribostamycin, but isomerase activity was not affected[3]. Drug-resistant strains of cocci and bacilli, as well as gram-positive and gram-negative cocci, can be effectively combatted with ribostamycin. Because it has enzymes that modify aminoglycosides, ribostamycin is particularly effective against the gentamicin-resistant bacteria Klebsiella pneumoniae[3]. |
| ln Vivo | The nephrotoxicity of ribostamycin and gentamicin was compared by urinalysis using 18 parameters. When a dose of 40 mg/kg per day was administered intramuscularly to Fischer rats for 14 days, ribostamycin caused little change of parameters in urine volume, urine osmolality, urine protein, maltase and beta 2-microglobulin. A slight increase with ribostamycin was observed in alpha-fucosidase, beta-N-acetylglucosaminidase, leucine aminopeptidase, lactic dehydrogenase (LDH) and potassium, and a moderate increase was observed in acid phosphatase and alkaline phosphatase. On the other hand, gentamicin caused a large alteration in most parameters. Both antibiotics caused a change of the isoenzyme pattern of LDH1-5, but the pattern with ribostamycin was much closer to the normal pattern than with gentamicin. When a dose of 80 mg/kg of ribostamycin was compared with 10 mg/kg of gentamicin, alteration of urinary parameters was almost comparable. Histopathological observations of the kidney specimens of rats given 40 mg/kg per day showed no histological damage with ribostamycin except for a slight increase and enlargement of lysosomes of the proximal epithelial cells. However, significant histological damage was observed with gentamicin, consistent with the results obtained from urinalysis. Renal accumulation of ribostamycin at a single dose of 20 mg/kg was three times less than that of gentamicin. Ribostamycin caused slightly less nephrotoxicity in rats than kanamycin and far less than dibekacin at an equal dosage of 40 mg/kg per day for 14 days [4]. |
| Enzyme Assay | In the process of screening of proteins binding to ribostamycin in bovine liver using the affinity column chromatography, we found that ribostamycin inhibited the chaperone activity of protein disulfide isomerase (PDI), but it did not inhibit the isomerase activity. PDI was identified by SDS-PAGE, Western blotting, and N-terminal amino acid sequence analysis. A 100:1 molar ratio of ribostamycin to PDI was almost sufficient to completely inhibit the chaperone activity of PDI. The binding affinity of ribostamycin to purified bovine PDI was determined by the Biacore system, which gave a K(D) value of 3.19 x 10(-4) M. This suggests that ribostamycin binds to region distinct from the CGHC motif of PDI. This is the first report to describe the inhibitor of the chaperone activity of PDI[3]. |
| Animal Protocol | The nephrotoxicity of ribostamycin and gentamicin was compared by urinalysis using 18 parameters. When a dose of 40 mg/kg per day was administered intramuscularly to Fischer rats for 14 days, ribostamycin caused little change of parameters in urine volume, urine osmolality, urine protein, maltase and beta 2-microglobulin. A slight increase with ribostamycin was observed in alpha-fucosidase, beta-N-acetylglucosaminidase, leucine aminopeptidase, lactic dehydrogenase (LDH) and potassium, and a moderate increase was observed in acid phosphatase and alkaline phosphatase. On the other hand, gentamicin caused a large alteration in most parameters. Both antibiotics caused a change of the isoenzyme pattern of LDH1-5, but the pattern with ribostamycin was much closer to the normal pattern than with gentamicin. When a dose of 80 mg/kg of ribostamycin was compared with 10 mg/kg of gentamicin, alteration of urinary parameters was almost comparable. Histopathological observations of the kidney specimens of rats given 40 mg/kg per day showed no histological damage with ribostamycin except for a slight increase and enlargement of lysosomes of the proximal epithelial cells. However, significant histological damage was observed with gentamicin, consistent with the results obtained from urinalysis. Renal accumulation of ribostamycin at a single dose of 20 mg/kg was three times less than that of gentamicin. Ribostamycin caused slightly less nephrotoxicity in rats than kanamycin and far less than dibekacin at an equal dosage of 40 mg/kg per day for 14 days. [4] |
| Toxicity/Toxicokinetics |
rat LD50 oral >7 gm/kg Drugs in Japan, 6(885), 1982 rat LD50 intraperitoneal 3080 mg/kg Japan Medical Gazette., 10(2)(5), 1973 rat LD50 subcutaneous 5600 mg/kg Iyakuhin Kenkyu. Study of Medical Supplies., 4(90), 1973 rat LD50 intravenous 375 mg/kg Japan Medical Gazette., 10(2)(5), 1973 rat LD50 intramuscular 2030 mg/kg Drugs in Japan, 6(885), 1982 |
| References |
[1]. Ribostamycin, as an intermediate in the biosynthesis of neomycin. J Antibiot (Tokyo). 1977 Sep;30(9):720-3. [2]. In vitro activity of mezlocillin, meropenem, aztreonam, vancomycin, teicoplanin, ribostamycin and fusidic acid against Borrelia burgdorferi. Int J Antimicrob Agents. 2001 Mar;17(3):203-8. [3]. Ribostamycin inhibits the chaperone activity of protein disulfide isomerase. Biochem Biophys Res Commun. 2001 Dec 21;289(5):967-72. [4]. Comparative nephrotoxicity of ribostamycin and gentamicin in rats evaluated by urinalysis. Drugs Exp Clin Res. 1989;15(6-7):273-89. |
| Additional Infomation |
A mutant of a neomycin-producting Streptomyces fradiae was found which synthesizes ribostamycin instead of neomycin. After a reverse mutation new colonies were obtained producting neomycin again. Ribostamycin might thus be considered as an intermediate in the biosynthesis of neomycin. [1] The in vitro susceptibility profile of Borrelia burgdorferi is not yet well defined for several antibiotics. Our study explored the in vitro susceptibility of B. burgdorferi to mezlocillin, meropenem, aztreonam, vancomycin, teicoplanin, ribostamycin and fusidic acid. Minimal inhibitory concentrations (MICs) and minimal borreliacidal concentrations (MBCs) were measured using a standardised colorimetric microdilution method and conventional subculture experiments. MIC values were lowest for mezlocillin (MIC(90), < or =0.06 mg/l) and meropenem (MIC(90), 0.33 mg/l). Vancomycin (MIC(90), 0.83 mg/l) was less effective in vitro. Borreliae proved to be resistant to aztreonam (MIC(90), >32 mg/l), teicoplanin (MIC(90), 6.6 mg/l), ribostamycin (MIC(90), 32 mg/l), and fusidic acid (MIC(90), >4 mg/l). The mean MBCs resulting in 100% killing of the final inoculum after 72 h of incubation were lowest for mezlocillin (MBC, 0.83 mg/l). This study gathered further data on the in vitro susceptibility patterns of the B. burgdorferi complex. The excellent in vitro effectiveness of acylamino-penicillin derivatives and their suitability for the therapy of Lyme disease is emphasised. [2] |
Solubility Data
| Solubility (In Vitro) |
H2O : 100~130 mg/mL (~235.27 mM ) DMSO : < 1 mg/mL |
| Solubility (In Vivo) |
Solubility in Formulation 1: 50 mg/mL (90.49 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.8098 mL | 9.0490 mL | 18.0979 mL | |
| 5 mM | 0.3620 mL | 1.8098 mL | 3.6196 mL | |
| 10 mM | 0.1810 mL | 0.9049 mL | 1.8098 mL |