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

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

Volume: 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

Affiliation:

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

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

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.

Cite this article as:

Al-Balasa A. Qosay*, Hassana A. Mohammad, Al Jabala A. Ghazi, Al-Shar A. Nizar, Almaaytahb M. Ammar and El-Elimata Tamam, Novel Thiazole Carboxylic Acid Derivatives Possessing a “Zinc Binding Feature” as Potential Human Glyoxalase-I Inhibitors, Letters in Drug Design & Discovery 2017; 14 (11) . https://dx.doi.org/10.2174/1570180814666170306120954