VIRTUAL SCREENING OF INDONESIAN HERBAL DATABASE FOR DNA METHYLTRANSFERASE INHIBITORS


Igustingurah Raka Bhaskarawilaputraka, Azminah Azminah, Linda Erlina, Rezi Riadhi Syahdi, Arry Yanuar

Abstract


Objective: DNA hypermethylation is an abnormal epigenetic process catalyzed by DNA methyltransferase 1 (DNMT1). It is also one of the factors that cause non-communicable diseases such as cancer, diabetes, and other metabolic diseases. DNA hypermethylation can be reversed by suppressing DNMT1 activity using a DNMT inhibitor. This study was conducted to seek out inhibitor candidates among natural products.

Methods: The search for potential inhibitors was conducted through a virtual screening of the Indonesian Herbal Database using AutoDockVina as docking software. Twenty-five compounds known for their inhibitory activity against DNMT1 were used as actives and as a reference for generating decoys, which was done using the Directory of Useful Decoys, Enhanced.

Results: The 12 compounds with binding energies below the cutoff value were cassiamin C (A1), procyanidin B2 (B2), ent-epicatechin- (4alpha->8)-ent-epicatechin (C3), epicatechin-(4beta->8)-epicatechin-3-O-gallate (D4), neorhusflavanone (E5), 3-O-galloylepicatechin- (4beta->6)-epicatechin-3-O-gallate (F6), withanolide (G7), 3-O-galloylepigallocatechin-(4beta->6)-epigallocatechin-3-O-gallate (H8), cyanidin 3-(6’’-caffeylsophoroside)-5-glucoside (I9), epifriedelanol (J10), gallocatechin-(4alpha->8)-epicatechin (K11), and scutellarein 7-glucosyl-(1->4)- rhamnoside (L12). A1 had the lowest binding energy of −12.7 kcal/mol, whereas K11 had the highest of −11.5 kcal/mol.

Conclusions: The virtual screening yielded five potential DNMT1 inhibitors: Procyanidin B2, ent-epicatechin-(4alpha->8)-ent-epicatechin, epicatechin-(4beta->8)-epicatechin-3-O-gallate, neorhusflavanone, and cyanidin 3-(6’’-caffeylsophoroside)-5-glucoside.  


Keywords


Epigenetic, DNA methyltransferase inhibitor, Indonesian Herbal Database, Virtual screening, AutoDockVina.

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About this article

Title

VIRTUAL SCREENING OF INDONESIAN HERBAL DATABASE FOR DNA METHYLTRANSFERASE INHIBITORS

Keywords

Epigenetic, DNA methyltransferase inhibitor, Indonesian Herbal Database, Virtual screening, AutoDockVina.

DOI

10.22159/ajpcr.2017.v10s5.23120

Date

01-10-2017

Additional Links

Manuscript Submission

Journal

Asian Journal of Pharmaceutical and Clinical Research
Special Issue October 2017 [PTMDS 2017] Page: 153-157

Print ISSN

0974-2441

Online ISSN

2455-3891

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Authors & Affiliations

Igustingurah Raka Bhaskarawilaputraka
Department of Pharmacy, Faculty of Pharmacy, Universitas Indonesia, Depok, Indonesia.
Indonesia

Azminah Azminah
Department of Pharmacy, Faculty of Pharmacy, Universitas Indonesia, Depok, Indonesia.
Indonesia

Linda Erlina
Department of Pharmacy, Faculty of Pharmacy, Universitas Indonesia, Depok, Indonesia.
Indonesia

Rezi Riadhi Syahdi
Department of Pharmacy, Faculty of Pharmacy, Universitas Indonesia, Depok, Indonesia.
Indonesia

Arry Yanuar
Department of Pharmacy, Faculty of Pharmacy, Universitas Indonesia, Depok, Indonesia.
Indonesia


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