Design, synthesis, structure, in vitro cytotoxic activity evaluation and docking studies on target enzyme GSK-3β of new indirubin-3ʹ-oxime derivatives
2020; Nature Portfolio; Volume: 10; Issue: 1 Linguagem: Inglês
10.1038/s41598-020-68134-8
ISSN2045-2322
AutoresNguyen Trong Dan, Hoang Duc Quang, Vuong Van Truong, Đỗ Hữu Nghị, Nguyễn Mạnh Cường, To Dao Cuong, Trần Quốc Toàn, Long Giang Bạch, Nguyen Huu Thuan Anh, Nguyễn Thị, Ngo Thi Lan, Luu Van Chinh, Phạm Minh Quân,
Tópico(s)Cancer therapeutics and mechanisms
ResumoAbstract The addition of chalcone and amine components into indirubin-3′-oxime resulted in 15 new derivatives with high yields. Structures of new derivatives were also elucidated through 1D, 2D-NMR and HR-MS(ESI) spectra and X-ray crystallography. All designed compounds were screened for cytotoxic activity against four human cancer cell lines (HepG2, LU-1, SW480 and HL-60) and one human normal kidney cell line (HEK-293). Compound 6f exhibited the most marked cytotoxicity meanwhile cytotoxicity of compounds 6e , 6h and 6l was more profound toward cancer cell lines than toward normal cell. These new derivatives were further analyzed via molecular docking studies on GSK-3β enzyme. Docking analysis shows that most of the derivatives exhibited potential inhibition activity against GSK-3β with characteristic interacting residues in the binding site. The fast pulling of ligand scheme was then employed to refine the binding affinity and mechanism between ligands and GSK-3β enzyme. The computational results are expected to contribute to predicting enzyme target of the trial inhibitors and their possible interaction, from which the design of new cytotoxic agents could be created in the future.
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