Design, synthesis and biological evaluation of novel glyoxalase I inhibitors possessing diazenylbenzenesulfonamide moiety as potential anticancer agents

  • Bioorg Med Chem. 2020 Aug 15;28(16):115608. doi: 10.1016/j.bmc.2020.115608.
Buthina A Al-Oudat  1 ,  Hana'a M Jaradat  2 ,  Qosay A Al-Balas  2 ,  Nizar A Al-Shar'i  2 ,  Amanda Bryant-Friedrich  3 ,  Mel F Bedi  3
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 Medicinal and Biological Chemistry, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH 43606, USA.
PMID: 32690268 DOI: 10.1016/j.bmc.2020.115608
Abstract

The enzyme glyoxalase-I (Glo-I) is an essential therapeutic target in Cancer treatment. Significant efforts have been made to discover competitive inhibitors of Glo-I as potential Anticancer agents. Herein, we report the synthesis of a series of diazenylbenzenesulfonamide derivatives, their in vitro evaluation against Glo-I and the resulting structure-activity relationships. Among the compounds tested, compounds 9h and 9j exhibited the highest activity with IC50 1.28 µM and 1.13 µM, respectively. Docking studies to explore the binding mode of the compounds identified key moieties that may contribute to the observed activities. The active compounds will serve as suitable leads for further chemical optimization.

Keywords
Anticancer agents; Diazenylbenzenesulfonamide; Glyoxalase-I; Molecular docking; Zinc binding groups.
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