Design, synthesis, structure, in vitro cytotoxic activity evaluation and docking studies on target enzyme GSK-3β of new indirubin-3'-oxime derivatives.

التفاصيل البيبلوغرافية
العنوان:	Design, synthesis, structure, in vitro cytotoxic activity evaluation and docking studies on target enzyme GSK-3β of new indirubin-3'-oxime derivatives.
المؤلفون:	Dan NT; Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, 11307, Vietnam.; Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, 11307, Vietnam.; Vietnam-Russia Tropical Center, Nguyen Van Huyen, Nghia Do, Cau Giay, Hanoi, 11307, Vietnam., Quang HD; Vietnam-Russia Tropical Center, Nguyen Van Huyen, Nghia Do, Cau Giay, Hanoi, 11307, Vietnam., Van Truong V; Vietnam-Russia Tropical Center, Nguyen Van Huyen, Nghia Do, Cau Giay, Hanoi, 11307, Vietnam., Huu Nghi D; Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, 11307, Vietnam.; Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, 11307, Vietnam., Cuong NM; Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, 11307, Vietnam.; Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, 11307, Vietnam., Cuong TD; Faculty of Pharmacy, Phenikaa University, Yen Nghia, Ha Dong, Hanoi, 12116, Vietnam.; A&A Green Phoenix Group JSC, Phenikaa Research and Technology Institute (PRATI), No.167 Hoang Ngan, Trung Hoa, Cau Giay, Hanoi, 11313, Vietnam., Toan TQ; Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, 11307, Vietnam.; Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, 11307, Vietnam., Bach LG; NTT Hi-Tech Institute, Nguyen Tat Thanh University, Ho Chi Minh City, Vietnam.; Center of Excellence for Functional Polymers and NanoEngineering, Nguyen Tat Thanh University, Ho Chi Minh City, Vietnam., Anh NHT; NTT Hi-Tech Institute, Nguyen Tat Thanh University, Ho Chi Minh City, Vietnam.; Center of Excellence for Functional Polymers and NanoEngineering, Nguyen Tat Thanh University, Ho Chi Minh City, Vietnam., Mai NT; Laboratory of Theoretical and Computational Biophysics, Ton Duc Thang University, Ho Chi Minh City, Vietnam.; Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh City, Vietnam., Lan NT; Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, 11307, Vietnam.; Institute of Materials Science, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, 11307, Vietnam., Van Chinh L; Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, 11307, Vietnam. chinhluuvan@gmail.com.; Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, 11307, Vietnam. chinhluuvan@gmail.com., Quan PM; Institute of Natural Products Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, 11307, Vietnam. pham-minh.quan@inpc.vast.vn.; Graduate University of Science and Technology, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Cau Giay, Hanoi, 11307, Vietnam. pham-minh.quan@inpc.vast.vn.
المصدر:	Scientific reports [Sci Rep] 2020 Jul 10; Vol. 10 (1), pp. 11429. Date of Electronic Publication: 2020 Jul 10.
نوع المنشور:	Journal Article; Research Support, Non-U.S. Gov't
اللغة:	English
بيانات الدورية:	Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE
أسماء مطبوعة:	Original Publication: London : Nature Publishing Group, copyright 2011-
مواضيع طبية MeSH:	Drug Design, Glycogen Synthase Kinase 3 beta/chemistry , Indoles/chemistry , Oximes/chemistry, Antineoplastic Agents/pharmacology ; Catalytic Domain ; Cell Survival ; Chalcones/chemistry ; Computational Biology ; Crystallography, X-Ray ; HEK293 Cells ; HL-60 Cells ; Hep G2 Cells ; Humans ; Inhibitory Concentration 50 ; Ligands ; Magnetic Resonance Spectroscopy ; Mass Spectrometry ; Molecular Docking Simulation ; Oximes/pharmacology ; Protein Binding ; Protein Domains ; Spectrometry, Mass, Electrospray Ionization
مستخلص:	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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المشرفين على المادة:	0 (Antineoplastic Agents) 0 (Chalcones) 0 (Indoles) 0 (Ligands) 0 (Oximes) 0 (indirubin-3'-monoxime) EC 2.7.11.1 (GSK3B protein, human) EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
تواريخ الأحداث:	Date Created: 20200712 Date Completed: 20210111 Latest Revision: 20210710
رمز التحديث:	20221213
مُعرف محوري في PubMed:	PMC7351726
DOI:	10.1038/s41598-020-68134-8
PMID:	32651416
قاعدة البيانات:	MEDLINE

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تدمد:	2045-2322
DOI:	10.1038/s41598-020-68134-8