New Cholesteryl Ester Transfer Protein from Indonesian Herbal Plants as Candidate Treatment of Cardiovascular Disease

Ratih Dewi Yudhani; Khariz Fahrurrozi; Dono Indarto

doi:10.3889/oamjms.2022.10457

Authors

Ratih Dewi Yudhani Department of Pharmacology, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia; Biomedical Laboratory, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia https://orcid.org/0000-0001-6781-8251
Khariz Fahrurrozi Undergraduate Student, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia https://orcid.org/0000-0003-3276-6716
Dono Indarto Biomedical Laboratory, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia; Department of Physiology, Faculty of Medicine, Universitas Sebelas Maret, Surakarta, Indonesia https://orcid.org/0000-0001-7420-5816

DOI:

https://doi.org/10.3889/oamjms.2022.10457

Keywords:

Cardiovascular disease, Cholesterol ester transfer protein inhibitor, Molecular docking, Indonesian plants, Phytochemical screening, In silico

Abstract

BACKGROUND: There is a strong negative relationship between high-density lipoprotein cholesterol (HDL-C) and the risk of cardiovascular disease (CVD). Cholesterol ester transfer protein (CETP) is a glycoprotein transporter that transfers cholesterol esters to very low-density lipoprotein and low-density lipoprotein cholesterol (LDL-C). The CETP inhibitor is a new strategy against CVD because of its ability to increase HDL-C. Various Indonesian plants have not been optimally used, and in silico phytochemical screening of these plants showing potential as CETP inhibitors is still limited.

AIM: This study for exploring Indonesian phytochemicals as CETP inhibitors for new CVD treatments.

METHODS: We screened 457 phytochemicals registered in the herbal database and met Lipinski’s rule of five. Their molecular structures were downloaded from the PubChem database. The three-dimensional structures of CETP and dalcetrapib (the CETP inhibitor standard) were obtained from a protein data bank (http://www.rcsb.org/pdb/) with the 4EWS code and ZINC database with the ZINC03976476 code, respectively. CETP–dalcetrapib binding complexes were validated 5 times using AutoDock Vina 1.1.2 software. Interactions between CETP and phytochemicals were molecularly docked with the same software and visualized using Pymol 1.8× software.

RESULTS: Dalcetrapib had a docking score of −9.22 kcal/mol and bound to CETP at Ser230 and His232 residues. The 11 phytochemicals had lower binding scores than dalcetrapib, but only L-(+)-tartaric acid, chitranone, and oxoxylopine could interact with CETP at the Ser230 residue. These are commonly found in Tamarindus indica, Plumbago zeylanica, and Annona reticulata, respectively.

CONCLUSION: L-(+)-Tartaric acid, chitranone, and oxoxylopine show potential as CETP inhibitors in silico.

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