VIRTUAL SCREENING OF INDONESIAN HERBAL DATABASE FOR DNA METHYLTRANSFERASE INHIBITORS


AZMINAH AZMINAH

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.


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About this article

Title

VIRTUAL SCREENING OF INDONESIAN HERBAL DATABASE FOR DNA METHYLTRANSFERASE INHIBITORS

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

AZMINAH AZMINAH
Indonesia


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