Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Targeting GSK-3β enzyme by diazepino-quinolone derivatives

Lubna Swellmeen¹ , Haneen A Basheer², Amal Uzrail³, Haneen Sallam², Yusuf Al-Hiari⁴, Ahlam Alkilani²

¹Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Hashemite University, Zarqa, Jordan; ²Department of Pharmaceutical Sciences, Faculty of Pharmacy, Zarqa University, Zarqa 13132, Jordan; ³Department of Medical Analysis, Faculty of Sciences, Al-Albayt University, Jordan; ⁴Faculty of Pharmacy, The University of Jordan, Amman, Jordan.

For correspondence:- Lubna Swellmeen Email: lubnam@hu.edu.jo Tel:+962778004500

Accepted: 24 September 2022 Published: 28 October 2022

Citation: Swellmeen L, Basheer HA, Uzrail A, Sallam H, Al-Hiari Y, Alkilani A. Targeting GSK-3β enzyme by diazepino-quinolone derivatives. Trop J Pharm Res 2022; 21(10):2147-2151 doi: 10.4314/tjpr.v21i10.15

© 2022 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To synthesize a heterocyclic system containing quinolone and diazepine scaffolds as GSK-3β inhibitor.

Methods: The diazepino-quinoline derivatives were synthesized starting from quinolone nucleus in a simple chemical reaction. The in vitro GSK-3β enzyme assay and MTT assay against cancer cell lines were carried out followed by Z´Ä±-LYTE GSK-3β assay. Anticancer activity was determined using U-87 glioma cell line.

Results: Diazepino-quinoline derivatives were obtained in a good yield, and compound 102 exhibited significant activity against in vitro GSK-3β (IC₅₀: 0.114 μM), and anticancer activity (IC₅₀: 37 μM) against U-87 glioma cell line.

Conclusion: The GSK-3β enzyme is a potential target to treat different diseases, and diazepines derivatives are a successful template for inhibitors design against GSK-3β enzyme with IC₅₀ in a micromolar range.

Keywords: GSK-3β, Heterocyclic compounds, Quinolone, Benzodiazepine nucleus