Posters
Presentation Type
Poster
Discipline Track
Clinical Science
Abstract Type
Research/Clinical
Abstract
Background: Carbonic anhydrase (CA) II and IX are overexpressed in numerous tumors associated with the hypoxic phenotype and have been involved in poor prognosis and cancer progression, which characterizes them as an attractive therapeutic target. The purpose of this study was to identify sulfonamide analogues as CA inhibitors based on affinity and interactions of molecular docking.
Methods: Through structure and similarity-based virtual screening and applying filters involving a preselection based on functional group, Lipinski's rule of five, mutagenic and tumorigenic characteristics, the best candidates were docked into the isoenzymes. Known reference ligands were used to determine affinity regions favorable for protein-ligand interactions. The best scored sulfonamide derivatives with Tanimoto coefficient ≥ 0.7 were chosen for key interactions analysis. Finally, 10 available compounds for CA-II and 8 for CA-IX were selected for further investigation.
Results: Molecular docking into the protein binding pocket with 18 compounds for CA II/IX resulted in moderate to high binding affinity compared with reference ligands, but all of them higher than standard inhibitor acetazolamide. Key interactions with His94, His96, His119 coordinates ion Zn+2 in the active site, beside crucial H-bond with Thr199 and Thr200 for CA-II and Gln92 and Thr200 for CA-IX.
Conclusions: Selected compounds might be potential CA inhibitors based on good binding affinity and key interactions in the active site of crystallized structure after molecular docking.
Academic/Professional Position
Graduate Student
Recommended Citation
Valenzuela, Edilsa, "Ligand-based virtual screening of sulfonamide analogues for the discovery of new carbonic anhydrase II/IX inhibitors for cancer therapy" (2023). Research Symposium. 64.
https://scholarworks.utrgv.edu/somrs/theme1/posters/64
Included in
Ligand-based virtual screening of sulfonamide analogues for the discovery of new carbonic anhydrase II/IX inhibitors for cancer therapy
Background: Carbonic anhydrase (CA) II and IX are overexpressed in numerous tumors associated with the hypoxic phenotype and have been involved in poor prognosis and cancer progression, which characterizes them as an attractive therapeutic target. The purpose of this study was to identify sulfonamide analogues as CA inhibitors based on affinity and interactions of molecular docking.
Methods: Through structure and similarity-based virtual screening and applying filters involving a preselection based on functional group, Lipinski's rule of five, mutagenic and tumorigenic characteristics, the best candidates were docked into the isoenzymes. Known reference ligands were used to determine affinity regions favorable for protein-ligand interactions. The best scored sulfonamide derivatives with Tanimoto coefficient ≥ 0.7 were chosen for key interactions analysis. Finally, 10 available compounds for CA-II and 8 for CA-IX were selected for further investigation.
Results: Molecular docking into the protein binding pocket with 18 compounds for CA II/IX resulted in moderate to high binding affinity compared with reference ligands, but all of them higher than standard inhibitor acetazolamide. Key interactions with His94, His96, His119 coordinates ion Zn+2 in the active site, beside crucial H-bond with Thr199 and Thr200 for CA-II and Gln92 and Thr200 for CA-IX.
Conclusions: Selected compounds might be potential CA inhibitors based on good binding affinity and key interactions in the active site of crystallized structure after molecular docking.