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Eur J Med Chem. 2017 Dec 1;141:427-439. doi: 10.1016/j.ejmech.2017.09.016. Epub 2017 Oct 7.

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

Author information

1
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.
2
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; State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
3
State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
4
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. Electronic address: hongbowangyt@gmail.com.
5
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; State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China. Electronic address: beeyee_413@163.com.

Abstract

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.

KEYWORDS:

Apoptosis; Cancer; Synthesis; α-Hederagenin derivatives

PMID:
29040953
DOI:
10.1016/j.ejmech.2017.09.016
[Indexed for MEDLINE]

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