Background: Glyoxalase-I (Glo-I) enzyme is an attractive new target for developing new
cancer therapeutics. This enzyme is a dimeric mononuclear zinc coordinating metalloenzyme, and
the core zinc ion was utilized in designing potentially active inhibitors possessing a selective zinc
Objective: A panel of thiazole based carboxylic acid derivatives were designed, synthesized, and
evaluated for their in vitro inhibitory activity against Glo-I enzyme based on their chelating potential
with the zinc atom at the core of the active site.
Methods: Flexible molecular docking was employed in designing the proposed inhibitors. The designed
compounds were synthesized, fully characterized, and in vitro assayed against Glo-I enzyme.
Results: Compound 14 was identified as the most potent inhibitor of the series with an IC50 of
2.5 µM. Moreover, the in-silico calculated CDocker scores were in excellent agreement with the
experimental inhibitory activity of the compounds.
Conclusion: The carboxylic acid group was identified as an indispensable chelating functionality in
inhibiting Glo-I enzyme. The data obtained in this study indicate that these compounds could be
promising anti-cancer candidates and hence warrant further optimization.