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Synthetic Guaiacol Derivatives as Promising Myeloperoxidase Inhibitors Targeting Atherosclerotic Cardiovascular Disease
Author(s) -
Premkumar Jayaraj,
Sampath Parthasarathy,
Sanjay Rajagopalan,
Chandrakala Aluganti,
Rajagopal Desikan
Publication year - 2020
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202000084
Subject(s) - guaiacol , myeloperoxidase , chemistry , oxidative stress , pharmacology , inflammation , biochemistry , medicine , enzyme , immunology
Myeloperoxidase (MPO) is known to cause oxidative stress and inflammation leading to cardiovascular disease (CVD) complications. MPO‐mediated oxidation of lipoproteins leads to dysfunctional entities altering the landscape of lipoprotein functionality. The specificity of guaiacol derivatives toward preventing MPO‐mediated oxidation to limit MPO's harmful effects is unknown. Diligent in silico studies were accomplished for a portfolio of compounds with guaiacol as a building block. The compounds’ activity toward MPO inhibition was also validated. The role of these chemical entities in controlling MPO‐mediated oxidation of lipoproteins (LDL and HDL) was shown to agree with our approach of developing powerful MPO inhibitors. The mechanism of MPO inhibition was demonstrated to be reversible in nature. This study reveals that there is great potential for guaiacol derivatives as therapeutics for CVD by modulating lipid profiles, reducing atherosclerotic plaque burden, and subsequently optimizing cardiovascular functions.