2. Academic Validation
  3. Synthesis and biological evaluation of lovastatin-derived aliphatic hydroxamates that induce reactive oxygen species

Synthesis and biological evaluation of lovastatin-derived aliphatic hydroxamates that induce reactive oxygen species

  • Bioorg Med Chem Lett. 2016 Nov 15;26(22):5528-5533. doi: 10.1016/j.bmcl.2016.10.005.
Ruo-Kai Lin 1,  Yuh-Feng Lin 2,  Ming-Jen Hsu 3,  Chang-Lin Hsieh 4,  Chen-Yu Wang 5,  Chih-Chiang Huang 6,  Wei-Jan Huang 7
Affiliations

Affiliations

  • 1 Graduate Institute of Pharmacognosy, Taipei Medical University, 250 Wu-Xing Street, Taipei 110, Taiwan; Professional Master Program in Pharmaceutics and Biotechnology, 250 Wu-Xing Street, Taipei Medical University, Taipei 110, Taiwan; Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, Taipei Medical University, 250 Wu-Xing Street, Taipei 110, Taiwan.
  • 2 Division of Nephrology, Shuang Ho Hospital, 291 Zong-Zheng Road, New Taipei City 235, Taiwan.
  • 3 Department of Pharmacology, College of Medicine, Taipei Medical University, 250 Wu-Xing Street, Taipei 110, Taiwan.
  • 4 Professional Master Program in Pharmaceutics and Biotechnology, 250 Wu-Xing Street, Taipei Medical University, Taipei 110, Taiwan.
  • 5 TaiMed Biologics Inc., 607 Rui-Guang Road, Taipei 114, Taiwan.
  • 6 Graduate Institute of Pharmacognosy, Taipei Medical University, 250 Wu-Xing Street, Taipei 110, Taiwan.
  • 7 Graduate Institute of Pharmacognosy, Taipei Medical University, 250 Wu-Xing Street, Taipei 110, Taiwan; Ph.D. Program for the Clinical Drug Discovery from Botanical Herbs, Taipei Medical University, 250 Wu-Xing Street, Taipei 110, Taiwan; School of Pharmacy, National Defense Medical Center, 161 Section 6 Min-Quan East Road, Taipei 114, Taiwan. Electronic address: wjhuang@tmu.edu.tw.
PMID: 27756564 DOI: 10.1016/j.bmcl.2016.10.005
Abstract

Some hydroxamate compounds induce Cancer cell death by intracellular Reactive Oxygen Species (ROS). This study introduced the hydroxamate core into lovastatin, a fungus metabolite clinically used for the treatment of hypercholesterolemia. The resulting compounds were evaluated for the activity for inducing ROS production. Most compounds exhibited higher activity than original lovastatin. Of these compounds, compound 3c had the most potent activity. Test of cytotoxicity in a panel of human Cancer cell lines indicated compound 3c had activities superior to cisplatin in prostate Cancer PC-3 cells and breast Cancer T47D cells. In contrast, it in amounts up to 40μM had a much lower cytotoxic effect on normal human IMR-90 cells. Further profiling of cell cycle progression, cell Apoptosis, and DNA damage activated checkpoint signaling pathway revealed the important role of compound 3c-mediated cytotoxicity in ROS generation.

Keywords

Aliphatic hydroxamate; Fungus metabolite; Lovastatin; Reactive oxygen species.

Figures
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z