Thienamycin
* Please be kindly noted products are not for therapeutic use. We do not sell to patients.
Category | Antibiotics |
Catalog number | BBF-03126 |
CAS | 59995-64-1 |
Molecular Weight | 272.32 |
Molecular Formula | C11H16N2O4S |
Purity | > 95% |
Online Inquiry
Description
Thienamycin is a β-lactam antibiotic produced by Str. cattleya NRRL8057. Broad-spectrum antibacterial activity.
Specification
Synonyms | (5R,6S)-3-[(2-Aminoethyl)thio]-6-[(1R)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; [5R-[5α,6α(R*)]]-3-[(2-Aminoethyl)thio]-6-(1-hydroxyethyl)-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid; (+)-Thienamycin |
IUPAC Name | (5R,6S)-3-(2-aminoethylsulfanyl)-6-[(1R)-1-hydroxyethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid |
Canonical SMILES | CC(C1C2CC(=C(N2C1=O)C(=O)O)SCCN)O |
InChI | InChI=1S/C11H16N2O4S/c1-5(14)8-6-4-7(18-3-2-12)9(11(16)17)13(6)10(8)15/h5-6,8,14H,2-4,12H2,1H3,(H,16,17)/t5-,6-,8-/m1/s1 |
InChI Key | WKDDRNSBRWANNC-ATRFCDNQSA-N |
Properties
Appearance | White Solid |
Antibiotic Activity Spectrum | bacteria |
Boiling Point | 514.0±50.0°C at 760 mmHg |
Density | 1.5±0.1 g/cm3 |
Reference Reading
1. Thienamycin: development of imipenen-cilastatin
J Birnbaum, F M Kahan, J G Sundelof, H Kropp J Antimicrob Chemother . 1983 Dec;12 Suppl D:1-35. doi: 10.1093/jac/12.suppl_d.1.
Thienamycin, a natural product produced by Streptomyces cattleya is the first representative of a unique class of beta-lactam antibiotics, the carbapenems. Despite its outstanding potency and antibacterial spectrum, thienamycin was itself unsuited for further development because of its chemical instability in concentrated solution and in the solid state. Synthesis of the amidine derivative, N-formimidoyl thienamycin (imipenem, MK0787) resulted in a crystalline product with much improved stability and with antibacterial properties significantly superior to thienamycin. Imipenem has an unusually broad antimicrobial spectrum. A high order of bactericidal activity is found against Pseudomonas aeruginosa, Serratia, Bacteroides fragilis, enterococci and numerous other species intrinsically resistant to other antibiotics. Imipenem is refractory to hydrolysis by all important classes of bacterial beta-lactamases and thus exhibits no cross-resistance with penicillins or cephalosporins. Imipenem is distinguished from the new generation of extended-spectrum cephems by its unusually high potency against Gram-positive as well as Gram-negative organisms. Offsetting these excellent antimicrobial properties was an unusual susceptibility exhibited by imipenem to renal metabolism in animal species and in man. Very low urinary recoveries resulted without, however, any significant reduction in the serum half-life of imipenem. A brush-border dipeptidase, dehydropeptidase-I, was shown to be responsible for renal metabolism. Metabolism has been countered with the development of cilastatin (MK0791), a substituted amino-propenoate inhibitor of dehydropeptidase which is specific, potent and well matched in its pharmacokinetic properties for co-administration with imipenem. With the imipenem/cilastatin combination, uniformly high urinary concentrations and recovery are obtained regardless of the varying but often extensive metabolism suffered by imipenem in human populations. An additional benefit conferred by cilastatin results from its ability to exclude imipenem competitively from entry into and subsequent metabolism within the proximal tubular epithelium of the kidney. The tubular necrosis induced by imipenem alone when it is administered at very high doses to susceptible mammalian species is thereby eliminated. Thus the imipenem/cilastatin combination affords reliability and enhanced safety in the application of the antibiotic's unusual antibacterial potential in the treatment of difficult infections regardless of the site of disease.
2. A metallo-β-lactamase enzyme for internal detoxification of the antibiotic thienamycin
Didier Raoult, Pierre Pontarotti, Seydina M Diene, Linda Hadjadj, Eric Chabrière, Lucile Pinault, Sophie Alexandra Baron, Jean-Marc Rolain, Nicholas Armstrong, Saïd Azza Sci Rep . 2021 May 12;11(1):10062. doi: 10.1038/s41598-021-89600-x.
Thienamycin, the first representative of carbapenem antibiotics was discovered in the mid-1970s from soil microorganism, Streptomyces cattleya, during the race to discover inhibitors of bacterial peptidoglycan synthesis. Chemically modified into imipenem (N-formimidoyl thienamycin), now one of the most clinically important antibiotics, thienamycin is encoded by a thienamycin gene cluster composed of 22 genes (thnA to thnV) from S. cattleya NRRL 8057 genome. Interestingly, the role of all thn-genes has been experimentally demonstrated in the thienamycin biosynthesis, except thnS, despite its annotation as putative β-lactamase. Here, we expressed thnS gene and investigated its activities against various substrates. Our analyses revealed that ThnS belonged to the superfamily of metallo-β-lactamase fold proteins. Compared to known β-lactamases such as OXA-48 and NDM-1, ThnS exhibited a lower affinity and less efficiency toward penicillin G and cefotaxime, while imipenem is more actively hydrolysed. Moreover, like most MBL fold enzymes, additional enzymatic activities of ThnS were detected such as hydrolysis of ascorbic acid, single strand DNA, and ribosomal RNA. ThnS appears as a MBL enzyme with multiple activities including a specialised β-lactamase activity toward imipenem. Thus, like toxin/antitoxin systems, the role of thnS gene within the thienamycin gene cluster appears as an antidote against the produced thienamycin.
3. Antibacterial activity of imipenem: the first thienamycin antibiotic
L Gerckens, F M Kahan, J G Sundelof, H Kropp Rev Infect Dis . 1985 Jul-Aug;7 Suppl 3:S389-410. doi: 10.1093/clinids/7.supplement_3.s389.
Imipenem (N-formimidoyl thienamycin) is the first representative of a new class of beta-lactam antibiotics--the carbapenems. Imipenem has an unusually broad spectrum, high potency, and no cross-resistance with other beta-lactam antibiotics. Susceptible gram-negative species include Pseudomonas aeruginosa, Serratia, and Enterobacter. Activity is high against Staphylococcus aureus, most group D streptococci, and Staphylococcus epidermidis but is variable against methicillin-resistant S. aureus. Imipenem is more active against Bacteroides than are other beta-lactam agents, chloramphenicol, metronidazole, and clindamycin. The minimal inhibitory concentrations (MICs) for 98% of 30,655 isolates--excluding those of the three resistant species (Pseudomonas maltophilia, Pseudomonas cepacia, and Streptococcus faecium)--were less than 8 micrograms/ml, the susceptibility breakpoint adopted for clinical trials. Imipenem is bactericidal (minimal bactericidal concentrations (MBCs] less than twice the MICs). For P. aeruginosa, MBCs of imipenem are less influenced by high inoculum density rather than are MBCs of antipseudomonal penicillins and cephalosporins. Stability of imipenem to diverse classes of plasmid-mediated and chromosomal beta-lactamases accounts for its lack of cross-resistance with other beta-lactam antibiotics. Imipenem is also active against P. aeruginosa with non-lactamase-mediated resistance to classical beta-lactam agents. Efficacy of imipenem was shown in animal models, including septicemia in normal and neutropenic rodents and P. aeruginosa pneumonia. Imipenem also has a unique postantibiotic effect against P. aeruginosa in vivo.
Recommended Products
BBF-03755 | Actinomycin D | Inquiry |
BBF-02594 | Pyrrolnitrin | Inquiry |
BBF-00969 | Homomycin | Inquiry |
BBF-00693 | Ansamitocin P-3 | Inquiry |
BBF-05781 | Emodepside | Inquiry |
BBF-05843 | Bacitracin | Inquiry |
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 ╳