Investigation of HMG-CoA reductase inhibitory and antioxidant effects of various hydroxycoumarin derivatives.

Arch Pharm (Weinheim) 2020 Jul 10:e1900378. Epub 2020 Jul 10.

Department of Chemistry, Faculty of Arts and Sciences, Marmara University, Istanbul, Turkey.

Cardiovascular diseases are one of the primary causes of deaths worldwide, and the development of atherosclerosis is closely related to hypercholesterolemia. As the reduction of the low-density lipoprotein cholesterol level is critical for treating these diseases, the inhibition of 3-hydroxy-3-methyl-glutaryl coenzyme A (HMG-CoA) reductase, which is essentially responsible for cholesterol biosynthesis, stands out as a key solution to lower plasma cholesterol levels. In this study, we synthesized several dihydroxycoumarins and investigated their antioxidant and in vitro HMG-CoA reductase inhibitory effects. Furthermore, we carried out in silico studies and examined the quantum-chemical properties of the coumarin derivatives. We also performed molecular docking experiments and analyzed the binding strength of each coumarin derivative. Our results revealed that compound IV displayed the highest HMG-CoA reductase inhibitory activity (IC  = 42.0 µM) in vitro. Cupric-reducing antioxidant capacity and ferric-reducing antioxidant power assays demonstrated that coumarin derivatives exhibit potent antioxidant activities. Additionally, a close relationship was found between the lowest unoccupied molecular orbital energy levels and the antioxidant activities.

Download full-text PDF

Source
http://dx.doi.org/10.1002/ardp.201900378DOI Listing
July 2020

Publication Analysis

Top Keywords

hmg-coa reductase
16
reductase inhibitory
12
coumarin derivatives
8
antioxidant activities
8
antioxidant
6
studies examined
4
derivatives performed
4
quantum-chemical properties
4
properties coumarin
4
examined quantum-chemical
4
performed molecular
4
docking experiments
4
strength coumarin
4
coumarin derivative
4
binding strength
4
analyzed binding
4
silico studies
4
experiments analyzed
4
molecular docking
4
inhibitory effects
4

References

(Supplied by CrossRef)

Son M. et al.
J. Neurol. Sci. 2013

Yuce B. et al.
Drug Res. 2009

Stromgaard K. et al.
2009

Colle S. et al.
Bioorg. Med. Chem. 1999

Kleemann R. et al.
Cardiovasc. Hematol. Disord.: Drug Targets 2005

Similar Publications