Cardioprotective effect of novel sulphonamides-1,3,5-triazine conjugates against ischaemic-reperfusion injury via selective inhibition of MMP-9

Xiao-Zhu Zheng; Jia-Li Zhou; Jing Ye; Pei-Pei Guo; Chun-Shui Lin

doi:10.1111/cbdd.12807

Cardioprotective effect of novel sulphonamides-1,3,5-triazine conjugates against ischaemic-reperfusion injury via selective inhibition of MMP-9

Chem Biol Drug Des. 2016 Nov;88(5):756-765. doi: 10.1111/cbdd.12807. Epub 2016 Jul 15.

Authors

Xiao-Zhu Zheng^{1

2}, Jia-Li Zhou¹, Jing Ye², Pei-Pei Guo², Chun-Shui Lin³

Affiliations

¹ Department of Anesthesiology, Zhejiang Hospital, Hangzhou, Zhejiang, China.
² Department of Anesthesiology, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong, China.
³ Department of Anesthesiology, Nanfang Hospital of Southern Medical University, Guangzhou, Guangdong, China. linchunshui@hotmail.com.

PMID: 27317634
DOI: 10.1111/cbdd.12807

Abstract

Diseases affecting cardiovascular system are ranked as a top most cause of morbidity and mortality. Herein, a novel class sulphonamides-1,3,5-triazine conjugates have been synthesized and tested for inhibitory activity against MMP-2 and MMP-9. The results of the study showed that these molecules efficiently inhibit MMP-9 than MMP-2, revealing compound 8e as the most potent inhibitor (IC₅₀ = 2.34 ± 0.56 nm). Due to involvement of MMP-9 in many cardiovascular diseases, particularly in myocardial ischaemia (MI), compound 8e was further subjected for the determination of the protective effect on isoproterenol (ISO)-induced myocardial injury in rats.

Keywords: 1,3,5-triazine; MMP inhibition; biochemical assay; myocardial ischaemia; sulphonamide.

MeSH terms

Animals
Antioxidants / metabolism
Cardiotonic Agents / chemistry*
Cardiotonic Agents / metabolism
Cardiotonic Agents / pharmacology
Cardiotonic Agents / therapeutic use
Heart / drug effects
Inhibitory Concentration 50
Isoproterenol / toxicity
Male
Matrix Metalloproteinase 2 / chemistry
Matrix Metalloproteinase 2 / metabolism
Matrix Metalloproteinase 9 / chemistry
Matrix Metalloproteinase 9 / metabolism*
Matrix Metalloproteinase Inhibitors / chemistry*
Matrix Metalloproteinase Inhibitors / metabolism
Matrix Metalloproteinase Inhibitors / pharmacology
Matrix Metalloproteinase Inhibitors / therapeutic use
Myocardium / metabolism
Myocardium / pathology
Protein Binding
Rats
Rats, Wistar
Reperfusion Injury / chemically induced
Reperfusion Injury / drug therapy
Structure-Activity Relationship
Sulfonamides / chemistry
Triazines / chemistry*
Triazines / metabolism
Triazines / pharmacology
Triazines / therapeutic use

Substances

Antioxidants
Cardiotonic Agents
Matrix Metalloproteinase Inhibitors
Sulfonamides
Triazines
Matrix Metalloproteinase 2
Matrix Metalloproteinase 9
Isoproterenol