Sparsomycin
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| Category | Antibiotics |
| Catalog number | BBF-03457 |
| CAS | 1404-64-4 |
| Molecular Weight | 361.47 |
| Molecular Formula | C13H19N3O5S |
| Purity | >95% |
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Description
It is an anti-tumor drug produced by the strain of Str. sparsogenes var. sparsogenes NRRL 2940, Str. cuspidosporus B-79. It has the effect of anti-bacterial and a few fungi. 0.05 μg/mL of Sparsomycin can inhibit the synthesis of 50% KB cell protein, it has the inhibitory effect on 11 kinds of experimental tumor, such as sarcoma-180 solid type, sarcoma-180 ascites type and Eschericz ascites carcinoma.
Specification
| Synonyms | Upjohn Antibiotic 155b1t; 2-Propenamide, N-(1-(hydroxymethyl)-2-(((methylthio)methyl)sulfinyl)ethyl)-3-(1,2,3,4-tetrahydro-6-methyl-2,4-dioxo-5-pyrimidinyl)-, (S-(E))-; 2-Propenamide, N-[1-(hydroxymethyl)-2-[[(methylthio)methyl]sulfinyl]ethyl]-3-(1,2,3,4-tetrahydro-6-methyl-2,4-dioxo-5-pyrimidinyl)-, [R-[R*,S*-(E)]]-; (+)-Sparsomycin; NSC 059729 |
| Storage | Store at 2-8°C |
| IUPAC Name | (E)-N-[(2S)-1-hydroxy-3-[(R)-methylsulfanylmethylsulfinyl]propan-2-yl]-3-(6-methyl-2,4-dioxo-1H-pyrimidin-5-yl)prop-2-enamide |
| Canonical SMILES | CC1=C(C(=O)NC(=O)N1)C=CC(=O)NC(CO)CS(=O)CSC |
| InChI | InChI=1S/C13H19N3O5S2/c1-8-10(12(19)16-13(20)14-8)3-4-11(18)15-9(5-17)6-23(21)7-22-2/h3-4,9,17H,5-7H2,1-2H3,(H,15,18)(H2,14,16,19,20)/b4-3+/t9-,23+/m0/s1 |
| InChI Key | XKLZIVIOZDNKEQ-CLQLPEFOSA-N |
Properties
| Appearance | White Crystal |
| Application | Antibiotics, Antineoplastic |
| Antibiotic Activity Spectrum | Neoplastics (Tumor); Fungi |
| Melting Point | 208-209°C (dec.) |
| Density | 1.466 g/cm3 |
| Solubility | Soluble in Water |
Reference Reading
1. Structure-activity relationships of sparsomycin and its analogues. Inhibition of peptide bond formation in cell-free systems and of L1210 and bacterial cell growth
H C Ottenheijm, M Remacha, P Lelieveld, J H Colstee, J P Ballesta, L A van den Broek, D Vázquez, R M Liskamp J Med Chem . 1987 Feb;30(2):325-33. doi: 10.1021/jm00385a014.
The biological activity of 14 analogues of sparsomycin (1) was studied in cell-free systems of Escherichia coli, Saccharomyces cerevisiae, and Sulfolobus solfataricus by measuring the inhibition of protein synthesis. The inhibition of L1210 colony formation in soft agar and bacterial cell growth in solid as well as in liquid medium was also examined. Each analogue possesses not more than two structural modifications of the sparsomycin molecule. This enabled us to determine unambiguously several structural and stereochemical features that are required for an optimal biological activity in these assays. Sparsomycin, having the SCRS chirality, is the most potent of the four possible stereoisomers. The results obtained with compounds 5-7 indicate that the presence of an oxygen atom on the S (alpha) atom is essential. Substitution of the bivalent sulfur atom by a CH2 group (10) or of the SCH3 moiety by a Cl atom (12) affects the activity of the molecule partially. Compound 12 is surprisingly active against intact cells. Substitution of the C(6)-CH3 group by a H(14) reduces the activity of the molecule. Isomerization of the trans double bond into the cis double bond yields cis-sparsomycin (15), which is inactive. The hydrophobic derivatives 8, 9, and 11 are considerably more active than sparsomycin; thus the ribosomal binding site for sparsomycin may have a hydrophobic character.
2. Kinetics of inhibition of rabbit reticulocyte peptidyltransferase by anisomycin and sparsomycin
C Coutsogeorgopoulos, M Ioannou, D Synetos Mol Pharmacol . 1998 Jun;53(6):1089-96.
A detailed kinetic study was carried out on the inhibitory mechanisms of two eukaryotic peptidyltransferase drugs (I), anisomycin and sparsomycin. In an in vitro system from rabbit reticulocytes, AcPhe-puromycin is produced in a pseudo-first-order reaction from the preformed AcPhe-tRNA/poly(U)/80S ribosome complex (complex C) and excess puromycin (S). This reaction is inhibited by anisomycin and sparsomycin through different mechanisms. Anisomycin acts as a mixed noncompetitive inhibitor. The product, AcPhe-puromycin, is derived only from C according to the puromycin reaction. On the other hand, sparsomycin reacts with complex C in a two-step reaction, [REACTION; SEE TEXT] An initial rapid binding of the drug produces the encounter complex CI. During this step and before conversion of CI to C*I, sparsomycin behaves as a competitive inhibitor. The rapidly produced CI is isomerized slowly to a conformationally altered species C*I in which I is bound more tightly. The rate constants of this step are k6 = 2.1 min-1 and k7 = 0.095 min-1. Moreover, the low value of the association rate constant k7/Ki' (2 x 10(5) M-1 sec-1), provides insight into the rates of possible conformational changes occurring during protein synthesis and supports the proposal that sparsomycin is the first example of a slow-binding inhibitor of eukaryotic peptidyltransferase. When complex C is preincubated with concentrations of sparsomycin of >8 Ki and then reacts with a mixture of puromycin and sparsomycin, the inhibition becomes linear mixed noncompetitive and involves C*I instead of CI. During this phase, AcPhe-puromycin is produced from a new, modified ribosomal complex with a lower catalytic rate constant. Thus, sparsomycin also acts as a modifier of eukaryotic peptidyltransferase activity.
3. Sparsomycin Exhibits Potent Antiplasmodial Activity In Vitro and In Vivo
Yoshifumi Nishikawa, Nanang Rudianto Ariefta, Baldorj Pagmadulam, Coh-Ichi Nihei Pharmaceutics . 2022 Feb 28;14(3):544. doi: 10.3390/pharmaceutics14030544.
The emerging spread of drug-resistant malaria parasites highlights the need for new antimalarial agents. This study evaluated the growth-inhibitory effects of sparsomycin (Sm), a peptidyl transferase inhibitor, againstPlasmodium falciparum3D7 (chloroquine-sensitive strain),P. falciparumK1 (resistant to multiple drugs, including chloroquine),P. yoelii17XNL (cause of uncomplicated rodent malaria) andP. bergheiANKA (cause of complicated rodent malaria). Using a fluorescence-based assay, we found that Sm exhibited half-maximal inhibitory concentrations (IC50) of 12.07 and 25.43 nM againstP. falciparum3D7 and K1, respectively. In vitro treatment ofP. falciparum3D7 with Sm at 10 or 50 nM induced morphological alteration, blocked parasites in the ring state and prevented erythrocyte reinvasion, even after removal of the compound. In mice infected withP. yoelii17XNL, the administration of 100 μg/kg Sm for 7 days did not affect parasitemia. Meanwhile, treatment with 300 μg/kg Sm resulted in a significantly lower parasitemia peak (18.85%) than that observed in the control group (40.13%). In mice infected withP. bergheiANKA, both four and seven doses of Sm (300 μg/kg) prolonged survival by 33.33%. Our results indicate that Sm has potential antiplasmodial activities in vitro and in vivo, warranting its further development as an alternative treatment for malaria.
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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
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g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
