2. Academic Validation
  3. Lead optimization and biological evaluation of diazenylbenzenesulfonamides inhibitors against glyoxalase-I enzyme as potential anticancer agents

Lead optimization and biological evaluation of diazenylbenzenesulfonamides inhibitors against glyoxalase-I enzyme as potential anticancer agents

  • Bioorg Chem. 2022 Mar;120:105657. doi: 10.1016/j.bioorg.2022.105657.
Buthina A Al-Oudat 1,  Nizar A Al-Shar'i 2,  Qosay A Al-Balas 2,  Suaad A Audat 3,  Mohammad A Y Alqudah 4,  Ali H Hamzah 5,  Ramez W Hallak 5,  Mel Bedi 5,  Amanda Bryant-Friedrich 5
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan. Electronic address: [email protected].
  • 2 Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan.
  • 3 Department of Chemistry, College of Science and Arts, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan.
  • 4 Department of Clinical Pharmacy, College of Pharmacy, Jordan University of Science and Technology, P.O. Box 3030, Irbid 22110, Jordan.
  • 5 Department of Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH 43606, USA.
PMID: 35152183 DOI: 10.1016/j.bioorg.2022.105657
Abstract

In a previous report, we described the discovery of (E)-5-((8-hydroxyquinolin-5-yl)diazenyl)-2-methylbenzenesulfonamide as a potent inhibitor of GLO-I Enzyme with IC50 of 1.28 ± 0.12 μM. Herein, lead optimization of this compound was achieved through targeting the central zinc atom and hydrophilic amino acid residues in the active site of the Enzyme. Among the synthesized compounds, compound TS010 showed the most potent inhibitory activity with IC50 of 0.57 ± 0.04 μM. Compound TS013 also showed comparable activity to that of the lead compound with IC50 of 1.14 ± 0.03 μM. Molecular docking studies disclosed the binding mode of the compounds inside the active side of GLO-I Enzyme.

Keywords

Anticancer; Glyoxalase-I; Lead Optimization; MM-PBSA; Molecular Docking.

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