Cyclothialidine E
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| Category | Enzyme inhibitors |
| Catalog number | BBF-01122 |
| CAS | 194276-79-4 |
| Molecular Weight | 611.63 |
| Molecular Formula | C25H33N5O11S |
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Description
It is produced by the strain of Streptomyces sp. NR 0659. It and its homologues inhibit escherichia coli DNA helicases with IC50 of 0.7 μmol/L, and the reference neomycin was 1.2 μmol/L.
Specification
| IUPAC Name | (4S)-4-amino-5-[(2S,3R)-2-[[(5S,8S)-5-carbamoyl-14,16-dihydroxy-13-methyl-7,11-dioxo-10-oxa-3-thia-6-azabicyclo[10.4.0]hexadeca-1(16),12,14-trien-8-yl]carbamoyl]-3-hydroxypyrrolidin-1-yl]-5-oxopentanoic acid |
| Canonical SMILES | CC1=C2C(=C(C=C1O)O)CSCC(NC(=O)C(COC2=O)NC(=O)C3C(CCN3C(=O)C(CCC(=O)O)N)O)C(=O)N |
| InChI | InChI=1S/C25H33N5O11S/c1-10-16(32)6-17(33)11-8-42-9-14(21(27)36)29-22(37)13(7-41-25(40)19(10)11)28-23(38)20-15(31)4-5-30(20)24(39)12(26)2-3-18(34)35/h6,12-15,20,31-33H,2-5,7-9,26H2,1H3,(H2,27,36)(H,28,38)(H,29,37)(H,34,35)/t12-,13-,14+,15+,20-/m0/s1 |
| InChI Key | PVRMXRCYXJPYJV-OFCPVLAQSA-N |
Properties
| Solubility | Soluble in Water, Methanol |
Reference Reading
1. Discovery of novel DNA gyrase inhibitors by high-throughput virtual screening
David A Ostrov, José A Hernández Prada, Patrick E Corsino, Kathryn A Finton, Nhan Le, Thomas C Rowe Antimicrob Agents Chemother. 2007 Oct;51(10):3688-98. doi: 10.1128/AAC.00392-07. Epub 2007 Aug 6.
The bacterial type II topoisomerases DNA gyrase and topoisomerase IV are validated targets for clinically useful quinolone antimicrobial drugs. A significant limitation to widely utilized quinolone inhibitors is the emergence of drug-resistant bacteria due to an altered DNA gyrase. To address this problem, we have used structure-based molecular docking to identify novel drug-like small molecules that target sites distinct from those targeted by quinolone inhibitors. A chemical ligand database containing approximately 140,000 small molecules (molecular weight, <500) was molecularly docked onto two sites of Escherichia coli DNA gyrase targeting (i) a previously unexplored structural pocket formed at the dimer interface of subunit A and (ii) a small region of the ATP binding pocket on subunit B overlapping the site targeted by coumarin and cyclothialidine drugs. This approach identified several small-molecule compounds that inhibited the DNA supercoiling activity of purified E. coli DNA gyrase. These compounds are structurally unrelated to previously identified gyrase inhibitors and represent potential scaffolds for the optimization of novel antibacterial agents that act on fluoroquinolone-resistant strains.
2. Cyclothialidine analogs, novel DNA gyrase inhibitors
K Yamaji, M Masubuchi, F Kawahara, Y Nakamura, A Nishio, S Matsukuma, M Fujimori, N Nakada, J Watanabe, T Kamiyama J Antibiot (Tokyo). 1997 May;50(5):402-11. doi: 10.7164/antibiotics.50.402.
DNA gyrase inhibitors, cyclothialidines B, C, D and E were isolated from four Streptomycete strains (NR 0659, NR 0660, NR 0661 and NR 0662). Their structures have been elucidated based on the amino acid analysis of the hydrolysates, NMR and HRFAB-MS experiments and shown to be cyclothialidine analogs. The absolute stereochemistry has been determined by the chiral HPLC analysis of the hydrolysates. Cyclothialidines B, D and E are novel and potent inhibitors of DNA gyrase.
3. Effect of different classes of inhibitors on DNA gyrase from Mycobacterium smegmatis
M Chatterji, S Unniraman, S Mahadevan, V Nagaraja J Antimicrob Chemother. 2001 Oct;48(4):479-85. doi: 10.1093/jac/48.4.479.
Quinolones, coumarins, cyclothialidines, CcdB and microcin B17 inhibit DNA gyrase. Information regarding these various inhibitors comes from studies performed with the enzyme from Escherichia coli, and subsequent analyses have also primarily been confined to this system. We have carried out a detailed analysis of the effect of various groups of inhibitors on Mycobacterium smegmatis gyrase and demonstrate differential susceptibility of the E. coli and M. smegmatis gyrases. Interestingly, M. smegmatis gyrase was refractory to the plasmid-borne proteinaceous inhibitors CcdB and microcin B17. Ciprofloxacin, a fluoroquinolone, showed a 10-fold reduction in efficacy against M. smegmatis compared with E. coli gyrase. We have also shown that etoposide, an antineoplastic drug, inhibits DNA gyrase activity by trapping the gyrase-DNA complex. DNA gyrases from both E. coli and M. smegmatis were susceptible to etoposide at comparable levels.
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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 ╳
