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

ABSTRACT: New 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 IC_50s 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.

SUBMITTER: Saleh JS

PROVIDER: S-EPMC10538245 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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

Saleh Joseph S JS Abd El Hadi Soha R SR Ibrahim Hany S HS Elrazaz Eman Z EZ Abouzid Khaled A M KAM

BMC chemistry 20230927 1

New 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 IC<sub>50s</sub> 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. ...[more]

PMID: 37759329

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