Discovery of new potent inhibitors for carbonic anhydrase IX by structure-based virtual screening

Liyan Wang; Chunmei Yang; Weiqiang Lu; Li Liu; Rui Gao; Sha Liao; Zhenjiang Zhao; Lili Zhu; Yufang Xu; Honglin Li; Jin Huang; Weiping Zhu

doi:10.1016/j.bmcl.2013.04.048

Discovery of new potent inhibitors for carbonic anhydrase IX by structure-based virtual screening

Bioorg Med Chem Lett. 2013 Jun 15;23(12):3496-9. doi: 10.1016/j.bmcl.2013.04.048. Epub 2013 Apr 29.

Authors

Liyan Wang¹, Chunmei Yang, Weiqiang Lu, Li Liu, Rui Gao, Sha Liao, Zhenjiang Zhao, Lili Zhu, Yufang Xu, Honglin Li, Jin Huang, Weiping Zhu

Affiliation

¹ State Key Laboratory of Bioreactor Engineering, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.

PMID: 23664215
DOI: 10.1016/j.bmcl.2013.04.048

Abstract

Through structure-based virtual screening, some dozen of benzene sulfonamides with novel scaffolds are identified as potent inhibitors against carbonic anhydrase (CA) IX with IC50 values ranging from 2.86 to 588.34 nM. Among them, compounds 1 and 9 show high selectivity against tumor-target CA IX over CA II (the selectivity ratios are 21.3 and 136.6, respectively). The possible binding poses of hit compounds are also explored and the selectivity is elucidated by molecular docking simulations. The hit compounds discovered in this work would provide novel scaffolds for further hit-to-lead optimization.

Publication types

Letter
Research Support, Non-U.S. Gov't

MeSH terms

Carbonic Anhydrase Inhibitors / chemistry*
Carbonic Anhydrase Inhibitors / pharmacology*
Drug Evaluation, Preclinical / methods
Humans
Molecular Docking Simulation
Structure-Activity Relationship
Sulfonamides / chemistry*
Sulfonamides / pharmacology*

Substances

Carbonic Anhydrase Inhibitors
Sulfonamides