Publication: Synthesis and evaluation of tetrahydrobenzo[cd]indole derivatives as glycogen phosphorylase inhibitors
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Issued Date
2025-04-01
Resource Type
ISSN
10542523
eISSN
15548120
Scopus ID
2-s2.0-85217757104
Journal Title
Medicinal Chemistry Research
Volume
34
Issue
4
Start Page
870
End Page
881
Rights Holder(s)
SCOPUS
Bibliographic Citation
Medicinal Chemistry Research Vol.34 No.4 (2025) , 870-881
Suggested Citation
Arunrattiyakorn P., Juiprasert C., Koulas S.M., Boonsri P., Aree T., Yagi-Utsumi M., Kato K., Leonidas D.D. Synthesis and evaluation of tetrahydrobenzo[cd]indole derivatives as glycogen phosphorylase inhibitors. Medicinal Chemistry Research Vol.34 No.4 (2025) , 870-881. 881. doi:10.1007/s00044-025-03384-7 Retrieved from: https://hdl.handle.net/20.500.14740/20629
Corresponding Author(s)
Other Contributor(s)
Abstract
A series of tetrahydrobenzo[cd]indole derivatives was synthesized by condensation of a fungal metabolite hyphodermin A, a naphtho[1,2-c]furan-3,9-dione derivative, and various anilines in methanol. Using this approach, ten analogs (3a–3j) were synthesized and tested as inhibitors against glycogen phosphorylase (GP). While compounds 3e and 3i bearing hydrophobic bromo and trifluoromethyl groups showed moderated inhibition (Ki = 32.3–57.4 μΜ), compound 3g with hydroxy group had the most potent activity with a Ki value of 7.9 ± 0.7 μΜ against human liver GPa. An X-ray crystallography study of the rabbit muscle GPb-3g complexes revealed that this inhibitor binds at a subsite within the indole binding site of GP which has not been previously observed to bind ligands. (Figure presented.)