6PGX

Synthesis of novel tellurides bearing benzensulfonamide moiety as carbonic anhydrase inhibitors with antitumor activity


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.36 Å
  • R-Value Free: 0.152 
  • R-Value Work: 0.118 
  • R-Value Observed: 0.119 

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Literature

Synthesis of novel tellurides bearing benzensulfonamide moiety as carbonic anhydrase inhibitors with antitumor activity.

Tanini, D.Ricci, L.Capperucci, A.Di Cesare Mannelli, L.Ghelardini, C.Peat, T.S.Carta, F.Angeli, A.Supuran, C.T.

(2019) Eur J Med Chem 181: 111586-111586

  • DOI: https://doi.org/10.1016/j.ejmech.2019.111586
  • Primary Citation of Related Structures:  
    6PGX

  • PubMed Abstract: 

    We have synthetized a novel series of β-hydroxy tellurides bearing the benzenesulfonamide group as potent inhibitors of carbonic anhydrase enzymes. In a one pot procedure, we discovered both the ring opening reaction of the three-membered ring and the cleavage of the sulfonamide protecting moiety at the same time. Moreover, the first X-ray co-crystallographic structure of a β-hydroxy telluride derivative with hCA II is reported. The potent effects of these compounds against the tumor-associated hCA IX with low nanomolar constant inhibition values give the possibility to evaluate their activity in vitro using a breast cancer cell line (MDA-MB-231). Compounds 7e and 7g induced significant toxic effects against tumor cells after 48 h incubation in normoxic conditions killing over 50% of tumor cells at 3 μM, but their efficacy decreased in hypoxic conditions reaching the 50% of the tumor cell viability only at 30 μM. These unusual features make them interesting lead compounds to act as antitumor agents, not only as Carbonic Anhydrase IX inhibitors, but reasonably in different pathways, where hCA IX is not overexpressed.


  • Organizational Affiliation

    University of Florence, Department of Chemistry "Ugo Schiff", Via della Lastruccia 3-13, I-50019, Sesto Fiorentino, Italy.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Carbonic anhydrase 2260Homo sapiensMutation(s): 0 
Gene Names: CA2
EC: 4.2.1.1
UniProt & NIH Common Fund Data Resources
Find proteins for P00918 (Homo sapiens)
Explore P00918 
Go to UniProtKB:  P00918
PHAROS:  P00918
GTEx:  ENSG00000104267 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00918
Sequence Annotations
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  • Reference Sequence
Small Molecules
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.36 Å
  • R-Value Free: 0.152 
  • R-Value Work: 0.118 
  • R-Value Observed: 0.119 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.458α = 90
b = 41.38β = 104.41
c = 72.43γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing

Structure Validation

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Entry History 

Deposition Data

  • Released Date: 2019-08-21 
  • Deposition Author(s): Peat, T.S.

Revision History  (Full details and data files)

  • Version 1.0: 2019-08-21
    Type: Initial release
  • Version 1.1: 2023-10-11
    Changes: Data collection, Database references, Refinement description