Insight into the mechanism of polyphenols on the activity of HMGR by molecular docking

Barira Islam, Charu Sharma, Abdu Adem, Elhadi Aburawi, Shreesh Ojha

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Statins are hypolipidemic drugs that are effective in the treatment of hypercholesterolemia by attenuating cholesterol synthesis in the liver via competitive inhibition of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase. Recently, dietary changes associated with drug therapy have garnered attention as novel drugs to mitigate or ameliorate hypercholesterolemia. The present study was undertaken to observe different dietary polyphenols that can bind to the active site of HMGR and inhibit it. Results from the 12 dietary polyphenols tested reveal that polyphenols can bind to HMGR and block the binding of nicotinamide adenine dinucleotide phosphate (NADP+). We observed that the rigidity of phenolic rings prevents the polyphenols from docking to the enzyme activity site. The presence of an ester linkage between the phenolic rings in (–)-epigallocatechin-3-gallate (EGCG) and the alkyl chain in curcumin allows them to orient in the active site of the HMGR and bind to the catalytic residues. EGCG and curcumin showed binding to the active site residues with a low GRID score, which may be a potential inhibitor of HMGR. Kaempferol showed binding to HMG-CoA, but with low binding affinity. These observations provide a rationale for the consistent hypolipidemic effect of EGCG and curcumin, which has been previously reported in several epidemiological and animal studies. Therefore, this study substantiates the mechanism of polyphenols on the activity of HMGR by molecular docking and provides the impetus for drug design involving further structure–function relationship studies.

LanguageEnglish
Pages4943-4951
Number of pages9
JournalDrug Design, Development and Therapy
Volume9
DOIs
Publication statusPublished - 28 Aug 2015
Externally publishedYes

Fingerprint

Polyphenols
Curcumin
Catalytic Domain
Hypercholesterolemia
NADP
Hypolipidemic Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Drug Design
Coenzyme A
Epidemiologic Studies
Oxidoreductases
Esters
Cholesterol
Drug Therapy
Liver
Enzymes
Pharmaceutical Preparations
epigallocatechin gallate

Cite this

Islam, Barira ; Sharma, Charu ; Adem, Abdu ; Aburawi, Elhadi ; Ojha, Shreesh. / Insight into the mechanism of polyphenols on the activity of HMGR by molecular docking. In: Drug Design, Development and Therapy. 2015 ; Vol. 9. pp. 4943-4951.
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Insight into the mechanism of polyphenols on the activity of HMGR by molecular docking. / Islam, Barira; Sharma, Charu; Adem, Abdu; Aburawi, Elhadi; Ojha, Shreesh.

In: Drug Design, Development and Therapy, Vol. 9, 28.08.2015, p. 4943-4951.

Research output: Contribution to journalArticle

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T1 - Insight into the mechanism of polyphenols on the activity of HMGR by molecular docking

AU - Islam, Barira

AU - Sharma, Charu

AU - Adem, Abdu

AU - Aburawi, Elhadi

AU - Ojha, Shreesh

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