Design and Synthesis of Novel Xyloketal Derivatives and Their Protective Activities against H2O2-Induced HUVEC Injury

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Abstract

In this work, we designed and synthesized a series of amide derivatives ( 1– 13), benzoxazine derivatives ( 16– 28) and amino derivatives ( 29– 30) from xyloketal B. All 28 new derivatives and seven known compounds ( 14, 15, 31– 35) were evaluated for their protection against H ₂O ₂-induced HUVEC injury. 23 and 24 exhibited more potential protective activities than other derivatives; and the EC ₅₀ values of them and the leading compound 31 (xyloketal B) were 5.10, 3.59 and 15.97 μM, respectively. Meanwhile, a comparative molecular similarity indices analysis (CoMSIA) was constructed to explain the structural activity relationship of these xyloketal derivatives. This 3D QSAR model from CoMSIA suggested that the derived model exhibited good predictive ability in the external test-set validation. Derivative 24 fit well with the COMSIA map, therefore it possessed the highest activity of all compounds. Compounds 23, 24 and 31 (xyloketal B) were further to examine in the JC-1 mitochondrial membrane potential (MMP) assay of HUVECs using flow cytometry (FCM). The result indicated that 23 and 24 significantly inhibited H ₂O ₂-induced decrease of the cell mitochondrial membrane potential (ΔΨm) at 25 μM. Collectively, the protective effects of xyloketals on H ₂O ₂-induced endothelial cells may be generated from oxidation action by restraining ROS and reducing the MMP.

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Author and article information

Contributors

Orazio Taglialatela-Scafati: Role: Academic Editor

Journal

Journal ID (nlm-ta): Mar Drugs

Journal ID (iso-abbrev): Mar Drugs

Journal ID (publisher-id): marinedrugs

Title: Marine Drugs

Publisher: MDPI

ISSN (Electronic): 1660-3397

Publication date (Electronic): 12 February 2015

Publication date Collection: February 2015

Volume: 13

Issue: 2

Pages: 948-973

Affiliations

[1 ]School of Chemistry & Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China; E-Mails: lsxinhoho@ 123456gmail.com (S.L.); gdzdlr@ 123456163.com (R.L.); xuxianf@ 123456mail.sysu.edu.cn (X.X.); qiuliqin@ 123456mail.sysu.edu.cn (L.Q.)

[2 ]Institute of Biomedicine & Guangdong Provincial Key Laboratory of Bioengineering Medicine, Jinan University, Guangzhou 510632, China; E-Mail: txiangqi@ 123456jnu.edu.cn

[3 ]Department of Pharmacy, Jinan University, Guangzhou 510632, China

Author notes

[†]

These authors contributed equally to this work.

[* ]Author to whom correspondence should be addressed; E-Mail: cespjy@ 123456mail.sysu.edu.cn ; Tel./Fax: +86-20-84036554.

Article

Publisher ID: marinedrugs-13-00948

DOI: 10.3390/md13020948

PMC ID: 4344611

PubMed ID: 25686273

SO-VID: 22cdcdc9-67b3-4f9b-82c0-b673bd7d20b4

License:

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).