Submit Manuscript  

Article Details


Novel Thiazole Carboxylic Acid Derivatives Possessing a “Zinc Binding Feature” as Potential Human Glyoxalase-I Inhibitors

[ Vol. 14 , Issue. 11 ]

Author(s):

Qosay A. Al-Balasa, Mohammad A. Hassana, Ghazi A. Al Jabala, Nizar A. Al-Shar, Ammar M. Almaaytahb and Tamam El-Elimata   Pages 1324 - 1334 ( 11 )

Abstract:


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 binding feature.

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.

Keywords:

Computer aided drug design, glyoxalase-I, thiazole carboxylic acid, zinc binding feature, CDocker, anticancer.

Affiliation:

Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid,, Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid, Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid,, Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid,, Department of Pharmaceutical Technology, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid

Graphical Abstract:



Read Full-Text article