Fragment merging approach for design, synthesis, and biological assessment of urea/acetyl hydrazide clubbed thienopyrimidine derivatives as GSK-3β inhibitors-Reference-Cited by-同舟云学术

Fragment merging approach for design, synthesis, and biological assessment of urea/acetyl hydrazide clubbed thienopyrimidine derivatives as GSK-3β inhibitors

Published:2023-09-27 Issue:1 Volume:17 Page:
ISSN:2661-801X
Container-title:BMC Chemistry
language:en
Short-container-title:BMC Chemistry

Author:

Saleh Joseph S.,Abd El Hadi Soha R.,Ibrahim Hany S.,Elrazaz Eman Z.,Abouzid Khaled A. M.

Abstract

AbstractNew thienopyrimidine derivatives were designed and synthesized as GSK-3β inhibitors based on the structure of active binding site of GSK-3β enzyme. In this study, compounds 6b and 6a were found to be moderate GSK-3β inhibitors with IC50s 10.2 and 17.3 μM, respectively. Molecular docking study was carried out by docking the targeted compounds in the binding site of the GSK-3β enzyme using the MOE program. Moreover, ADME study was performed to predict certain pharmacokinetic properties. The results showed that all synthesized compounds may not be able to penetrate the blood brain barrier; so, the chances of CNS side effects are predicted to be low. CYP1D6 is predicted to be inhibited by compounds (5a, 5d, 6a, 9a and 9b), So drug-drug interactions are expected upon administration of these compounds. Graphical Abstract

Funder

Egyptian Russian University

Publisher

Springer Science and Business Media LLC

Subject

General Chemistry

Link

https://link.springer.com/content/pdf/10.1186/s13065-023-01026-w.pdf

Reference29 articles.

1. Matthews HK, Bertoli C, de Bruin RAM. Cell cycle control in cancer. Nat Rev Mol Cell Biol. 2021;23(1):74–88. https://doi.org/10.1038/s41580-021-00404-3.

2. Cell cycle. https://www.genome.gov/genetics-glossary/Cell-Cycle. Accessed 18 March 2023.

3. Kannaiyan R, Mahadevan D. A comprehensive review of protein kinase inhibitors for cancer therapy. Expert Rev Anticancer Ther. 2018;18(12):1249–70. https://doi.org/10.1080/14737140.2018.1527688.

4. Martinez A, Castro A, Dorronsoro I, Alonso M. Glycogen synthase kinase 3 (GSK-3) inhibitors as new promising drugs for diabetes, neurodegeneration, cancer, and inflammation. Med Res Rev. 2002;22(4):373–84. https://doi.org/10.1002/MED.10011.

5. Augello G, Emma MR, Cusimano A, Azzolina A, Montalto G, McCubrey JA, Cervello M. The role of GSK-3 in cancer immunotherapy: GSK-3 inhibitors as a new frontier in cancer treatment. Cells. 2020;9:1427. https://doi.org/10.3390/CELLS9061427.