Structural modification of luteolin from Flos Chrysanthemi leads to increased tumor cell growth inhibitory activity

Chao Yang; Hui Chen; Shihai Lu; Meng Zhang; Wei Tian; Mingping Wang; Ling Zhang; Yunlong Song; Aijun Shen; Youjun Zhou; Ju Zhu; Canhui Zheng

doi:10.1016/j.bmcl.2016.06.043

Structural modification of luteolin from Flos Chrysanthemi leads to increased tumor cell growth inhibitory activity

Bioorg Med Chem Lett. 2016 Aug 1;26(15):3464-7. doi: 10.1016/j.bmcl.2016.06.043. Epub 2016 Jun 16.

Authors

Chao Yang¹, Hui Chen², Shihai Lu¹, Meng Zhang¹, Wei Tian¹, Mingping Wang³, Ling Zhang¹, Yunlong Song¹, Aijun Shen⁴, Youjun Zhou⁵, Ju Zhu⁶, Canhui Zheng⁷

Affiliations

¹ School of Pharmacy, Second Military Medical University, Shanghai 200433, China.
² Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
³ School of Pharmacy, Second Military Medical University, Shanghai 200433, China; Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing, Jiangsu 210009, China.
⁴ State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
⁵ School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: zhouyoujun@smmu.edu.cn.
⁶ School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: zhuju@smmu.edu.cn.
⁷ School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: canhuizheng@smmu.edu.cn.

PMID: 27353532
DOI: 10.1016/j.bmcl.2016.06.043

Abstract

The luteolin from Flos Chrysanthemi was found to directly bind to the Bcl-2 protein and inhibit the tumor cell growth in our previous study. However, it has been shown to possess wide and week biological activities. In this study, a series of derivatives of luteolin were designed and synthesized, and their tumor cell growth inhibitory activities were evaluated against human leukemia cell line HL-60. The results showed that compounds 1B-2, 2A-3, and 2B-5, with hydrophobic substituted benzyl groups introduced to B ring and hydrogen or methyl introduced to 7-OH group of luteolin, exhibited the strongest inhibitory activity with the IC50 lower than 10μM, which were significantly more potent than luteolin. The studies presented here offer a good example for modifications of flavones to improve their tumor cell growth inhibitory activities.

Keywords: Anti-tumor; Bcl-2 protein; Flos Chrysanthemi; Luteolin; Structural modification.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antineoplastic Agents, Phytogenic / chemistry
Antineoplastic Agents, Phytogenic / isolation & purification
Antineoplastic Agents, Phytogenic / pharmacology*
Cell Proliferation / drug effects
Chrysanthemum / chemistry*
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
HL-60 Cells
Humans
Luteolin / chemistry
Luteolin / isolation & purification
Luteolin / pharmacology*
Molecular Structure
Structure-Activity Relationship

Substances

Antineoplastic Agents, Phytogenic
Luteolin