Synthesis and Biological Evaluation of Oxygen-containing Heterocyclic Ring-fused 23-Hydroxybetulinic Acid Derivatives as Antitumor Agents

Hengyuan Zhang; Fangzheng Li; Peiqing Zhu; Jie Liu; Hequan Yao; Jieyun Jiang; Wencai Ye; Xiaoming Wu; Jinyi Xu

doi:10.1111/cbdd.12543

Synthesis and Biological Evaluation of Oxygen-containing Heterocyclic Ring-fused 23-Hydroxybetulinic Acid Derivatives as Antitumor Agents

Hengyuan Zhang, Fangzheng Li, Peiqing Zhu, Jie Liu, Hequan Yao, Jieyun Jiang, Wencai Ye, Xiaoming Wu, Jinyi Xu

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

A collection of isoxazole and oxadiazole substituted 23-hydroxybetulinic acid (HBA) derivatives were designed, synthesized and evaluated for their antitumor activity. Most of the newly synthesized compounds exhibited more potent antiproliferative activity than patent compound 23-hydroxybetulinic acid, especially 13e and 14a were about four- to sevenfold more potent against all tested cancer cell lines than 23-hydroxybetulinic acid. Furthermore, the in vivo antitumor activity of 13e and 14a was validated in H22 liver cancer and B16 melanoma xenograft mouse models. The structure-activity relationships of these 23-hydroxybetulinic acid derivatives were also discussed based on the present investigation.

Original language	English
Pages (from-to)	424-431
Number of pages	8
Journal	Chemical Biology and Drug Design
Volume	86
Issue number	4
DOIs	https://doi.org/10.1111/cbdd.12543
State	Published - Oct 1 2015

Bibliographical note

Publisher Copyright:
© 2015 John Wiley & Sons A/S.

Keywords

23-hydroxybetulinic acid
antiproliferative activity
antitumor activity
heterocycle
isoxazole
oxadiazole

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Pharmacology
Drug Discovery
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1111/cbdd.12543

Cite this

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title = "Synthesis and Biological Evaluation of Oxygen-containing Heterocyclic Ring-fused 23-Hydroxybetulinic Acid Derivatives as Antitumor Agents",

abstract = "A collection of isoxazole and oxadiazole substituted 23-hydroxybetulinic acid (HBA) derivatives were designed, synthesized and evaluated for their antitumor activity. Most of the newly synthesized compounds exhibited more potent antiproliferative activity than patent compound 23-hydroxybetulinic acid, especially 13e and 14a were about four- to sevenfold more potent against all tested cancer cell lines than 23-hydroxybetulinic acid. Furthermore, the in vivo antitumor activity of 13e and 14a was validated in H22 liver cancer and B16 melanoma xenograft mouse models. The structure-activity relationships of these 23-hydroxybetulinic acid derivatives were also discussed based on the present investigation.",

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author = "Hengyuan Zhang and Fangzheng Li and Peiqing Zhu and Jie Liu and Hequan Yao and Jieyun Jiang and Wencai Ye and Xiaoming Wu and Jinyi Xu",

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language = "English",

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AU - Zhang, Hengyuan

AU - Li, Fangzheng

AU - Zhu, Peiqing

AU - Liu, Jie

AU - Yao, Hequan

AU - Jiang, Jieyun

AU - Ye, Wencai

AU - Wu, Xiaoming

AU - Xu, Jinyi

PY - 2015/10/1

Y1 - 2015/10/1

N2 - A collection of isoxazole and oxadiazole substituted 23-hydroxybetulinic acid (HBA) derivatives were designed, synthesized and evaluated for their antitumor activity. Most of the newly synthesized compounds exhibited more potent antiproliferative activity than patent compound 23-hydroxybetulinic acid, especially 13e and 14a were about four- to sevenfold more potent against all tested cancer cell lines than 23-hydroxybetulinic acid. Furthermore, the in vivo antitumor activity of 13e and 14a was validated in H22 liver cancer and B16 melanoma xenograft mouse models. The structure-activity relationships of these 23-hydroxybetulinic acid derivatives were also discussed based on the present investigation.

AB - A collection of isoxazole and oxadiazole substituted 23-hydroxybetulinic acid (HBA) derivatives were designed, synthesized and evaluated for their antitumor activity. Most of the newly synthesized compounds exhibited more potent antiproliferative activity than patent compound 23-hydroxybetulinic acid, especially 13e and 14a were about four- to sevenfold more potent against all tested cancer cell lines than 23-hydroxybetulinic acid. Furthermore, the in vivo antitumor activity of 13e and 14a was validated in H22 liver cancer and B16 melanoma xenograft mouse models. The structure-activity relationships of these 23-hydroxybetulinic acid derivatives were also discussed based on the present investigation.

KW - 23-hydroxybetulinic acid

KW - antiproliferative activity

KW - antitumor activity

KW - heterocycle

KW - isoxazole

KW - oxadiazole

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Synthesis and Biological Evaluation of Oxygen-containing Heterocyclic Ring-fused 23-Hydroxybetulinic Acid Derivatives as Antitumor Agents

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

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