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


Ozalp L., DANIŞ Ö., Yuce-Dursun B., DEMİR S., Gunduz C., OGAN A.

ARCHIV DER PHARMAZIE, vol.353, no.10, 2020 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 353 Issue: 10
  • Publication Date: 2020
  • Doi Number: 10.1002/ardp.201900378
  • Journal Name: ARCHIV DER PHARMAZIE
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chimica, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Veterinary Science Database
  • Keywords: antioxidant, coumarin, HMG-CoA reductase, lipid lowering, radical scavenging, MECHANISM, COUMARIN, DOCKING, ETHERS
  • Marmara University Affiliated: Yes

Abstract

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 compoundIVdisplayed the highest HMG-CoA reductase inhibitory activity (IC50 = 42.0 mu M) 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.