Title

Molecular docking based screening of triterpenoids as potential G-quadruplex stabilizing ligands with anti-cancer activity

Authors

Sittichai Sillapapongwarakorn¹, Somchai Yanarojana¹, Darawan Pinthong¹, Amnuay Thithapandha¹, Jiraporn Ungwitayatorn², Porntip Supavilai^1*

Affiliation

¹Department of Pharmacology, Faculty of Science, Mahidol University, 272 Rama 6 Road, Bangkok 10400, Thailand;

²Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudhaya Road, Bangkok 10400, Thailand;

Email

porntip.sup@mahidol.ac.th

Article Type

Hypothesis

Date

Received August 17, 2017; Revised August 30, 2017; Accepted September 2, 2017; Published September 30, 2017

Triterpenoids isolated from Ganoderma lucidum (GLTs) exhibit a broad spectrum of anti-cancer properties, including anti-proliferative, anti-metastatic and anti-angiogenic activities. Current research studies revealed the role by GLTs in inducing apoptosis and suppression of telomerase activity of cancer cells with much lower toxicity to healthy cells. Compounds selectively binding and stabilizing G-quadruplex structures could inhibit the telomerase or downregulate the oncogenes and may act as anti-cancer agents. Targeting human telomeric G-quadruplex DNA could be one of the mechanisms by which these GLTs exert anti-cancer activity. In this study, 208 GLTs were screened for ligands with high binding affinity and selectively to stabilize the pG4DNA by using the docking tool AutoDock4. The results showed that ganoderic acid A and ganoderic acid Df exhibit high binding affinity and selectively bind to the lateral groove of pG4DNA. Based on our findings, we suggest that the triterpenoid represents a new class of G-quadruplex groovebinding ligands and thus act as potential anti-cancer agents.

Keywords

Ganoderma lucidum, G-quadruplex, molecular docking, triterpenoids, virtual screening

Citation

Sillapapongwarakorn et al. Bioinformation 13(9): 284-292 (2017)

Edited by

P Kangueane

ISSN

0973-2063

Publisher

Biomedical Informatics

License

This is an Open Access article which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. This is distributed under the terms of the Creative Commons Attribution License.