1. Design, synthesis and biological evaluation of novel glyoxalase I inhibitors possessing diazenylbenzenesulfonamide moiety as potential anticancer agents.
- Author
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Al-Oudat BA, Jaradat HM, Al-Balas QA, Al-Shar'i NA, Bryant-Friedrich A, and Bedi MF
- Subjects
- Antineoplastic Agents chemistry, Enzyme Inhibitors chemistry, Humans, Lactoylglutathione Lyase metabolism, Molecular Docking Simulation, Structure-Activity Relationship, Sulfonamides chemistry, Benzenesulfonamides, Antineoplastic Agents pharmacology, Enzyme Inhibitors pharmacology, Lactoylglutathione Lyase antagonists & inhibitors, Sulfonamides pharmacology
- 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 IC
50 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (Copyright © 2020 Elsevier Ltd. All rights reserved.)- Published
- 2020
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