Synthesis and cytotoxic activity of madecassic acid-silybin conjugate compounds in liver cancer cells.

Autor:	Tran CV; Institute of Chemistry, Vietnam Academy of Science and Technology 18 Hoang Quoc Viet Road, Cau Giay Hanoi Vietnam tranvansungvhh@gmail.com.; Graduate University of Science and Technology, Vietnam Academy of Science and Technology 18 Hoang Quoc Viet Road, Cau Giay Hanoi Vietnam., Tran TTP; Institute of Chemistry, Vietnam Academy of Science and Technology 18 Hoang Quoc Viet Road, Cau Giay Hanoi Vietnam tranvansungvhh@gmail.com.; Graduate University of Science and Technology, Vietnam Academy of Science and Technology 18 Hoang Quoc Viet Road, Cau Giay Hanoi Vietnam., Nguyen AT; Institute of Chemistry, Vietnam Academy of Science and Technology 18 Hoang Quoc Viet Road, Cau Giay Hanoi Vietnam tranvansungvhh@gmail.com., Tran LV; Institute of Chemistry, Vietnam Academy of Science and Technology 18 Hoang Quoc Viet Road, Cau Giay Hanoi Vietnam tranvansungvhh@gmail.com., Pham NT; Institute of Chemistry, Vietnam Academy of Science and Technology 18 Hoang Quoc Viet Road, Cau Giay Hanoi Vietnam tranvansungvhh@gmail.com., Nguyen LT; Institute of Chemistry, Vietnam Academy of Science and Technology 18 Hoang Quoc Viet Road, Cau Giay Hanoi Vietnam tranvansungvhh@gmail.com., Nguyen DT; Institute of Chemistry, Vietnam Academy of Science and Technology 18 Hoang Quoc Viet Road, Cau Giay Hanoi Vietnam tranvansungvhh@gmail.com., Garrett MD; School of Biosciences, University of Kent Stacey Building, Canterbury Kent CT2 7NJ UK., Nguyen NT; Institute of Biotechnology, Vietnam Academy of Science and Technology 18 Hoang Quoc Viet Road, Cau Giay Hanoi Vietnam., Do TT; Institute of Biotechnology, Vietnam Academy of Science and Technology 18 Hoang Quoc Viet Road, Cau Giay Hanoi Vietnam., Serpell CJ; Department of Pharmaceutical and Biological Chemistry, School of Pharmacy, University College London 29-39 Brunswick Square London WC1N 1AX UK chris.serpell@ucl.ac.uk., Tran SV; Institute of Chemistry, Vietnam Academy of Science and Technology 18 Hoang Quoc Viet Road, Cau Giay Hanoi Vietnam tranvansungvhh@gmail.com.
Jazyk:	angličtina
Zdroj:	RSC medicinal chemistry [RSC Med Chem] 2024 Aug 02. Date of Electronic Publication: 2024 Aug 02.
DOI:	10.1039/d4md00170b
Abstrakt:	A series of 14 conjugates of 2α,3β,23-triacetyl-madecassic acid and silybin were designed and synthesized. The madecassic acid unit was linked to silybin either directly at position C-7 or C-3; or through an amino acid linker (glycine, β-alanine, or 11-aminoundecanoic acid) at position C-3. The conjugates were tested in vitro for their cytotoxic effect on HepG2 cells using the MTT assay. The results confirmed that the conjugated compounds demonstrated a stronger cytotoxic effect compared to the parent compounds. Of these compounds, the most promising conjugate, compound 8, was evaluated for cytotoxic activity in the additional Hep3B, Huh7, and Huh7R human hepatocellular carcinoma cell lines and also for cell cycle changes and induction of apoptosis in HepG2 cells. This compound caused a rapid and significant induction of caspase 3 activity and induced cell cycle arrest in the S phase - effects distinct from the activity of madecassic acid. This is the first study on the synthesis and cytotoxicity of madecassic acid-silybin conjugates, and of their testing against liver cancer cell lines and provides evidence for a distinct biological profile versus madecassic acid alone. Competing Interests: There is no conflict of interest to declare. (This journal is © The Royal Society of Chemistry.)
Databáze:	MEDLINE
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