Design, synthesis and biological evaluation of novel α-hederagenin derivatives with anticancer activity

Xian-xuan Liu; Yan-ting Yang; Xiao Wang; Kai-yi Wang; Jia-qi Liu; Lei Lei; Xiao-min Luo; Rong Zhai; Feng-hua Fu; Hong-bo Wang; Yi Bi

doi:10.1016/j.ejmech.2017.09.016

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Design, synthesis and biological evaluation of novel α-hederagenin derivatives with anticancer activity

Journal article

Peer reviewed

Design, synthesis and biological evaluation of novel α-hederagenin derivatives with anticancer activity

Xian-xuan Liu, Yan-ting Yang, Xiao Wang, Kai-yi Wang, Jia-qi Liu, Lei Lei, Xiao-min Luo, Rong Zhai, Feng-hua Fu, Hong-bo Wang, …

European journal of medicinal chemistry, Vol.141, pp.427-439

2017-12-01

DOI: https://doi.org/10.1016/j.ejmech.2017.09.016

PMID: 29040953

Abstract

Apoptosis

Cancer

Synthesis

α-Hederagenin derivatives

In an attempt to arrive at a more potent cytotoxic agent than the parent compound α-hederagenin (H), 24 α-hederagenin derivatives (5–8, 11–24, 27–28, 31–32, and 35–36) were synthesized in a concise and efficient strategy and screened for in vitro cytotoxicity against the human cancer cell lines MKN45 and KB. Among these compounds, the polyamine derivative 15 exhibited more potency than the parent compound with IC50 values in the range of 4.22 μM–8.05 μM. Compound 15 increased Bax/bcl-2 ratio that disrupted the mitochondrial potential and induced apoptosis. Therefore, the present studies highlight the importance of polyamine derivatives of α-hederagenin in the discovery and development of novel anticancer agents. [Display omitted] •Synthesis of 24 novel α-hederagenin derivatives.•α-Hederagenin derivative 15 was active against Hela (IC50 = 4.22 ± 0.15 μM) and KBV (IC50 = 8.05 ± 0.08 μM).•It was the first time to discovered that the active molecule induces apotosis through the mitochondrial pathway.

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Collaboration types: Domestic collaboration
Citation topics: 3 Agriculture, Environment & Ecology; 3.16 Phytochemicals; 3.16.211 Triterpenoids
Web Of Science research areas: Chemistry, Medicinal
ESI research areas: Chemistry

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Title: Design, synthesis and biological evaluation of novel α-hederagenin derivatives with anticancer activity
Creators: Xian-xuan Liu - School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, China
Yan-ting Yang - School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, China
Xiao Wang - School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, China
Kai-yi Wang - School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, China
Jia-qi Liu - School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, China
Lei Lei - School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, China
Xiao-min Luo - State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China
Rong Zhai - School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, China
Feng-hua Fu - School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, China
Hong-bo Wang - School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, China
Yi Bi - School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, 264005, China
Publication Details: European journal of medicinal chemistry, Vol.141, pp.427-439
Publisher: Elsevier Masson SAS
Academic Unit: Miller School of Medicine; Molecular and Cellular Pharmacology Research
Language: English
Resource Type: Journal article
PMID: 29040953
Record Identifier: 991031615004702976