Sillapapongwarakorn Sittichai, Yanarojana Somchai, Pinthong Darawan, Thithapandha Amnuay, Ungwitayatorn Jiraporn, Supavilai Porntip
Department of Pharmacology, Faculty of Science, Mahidol University, 272 Rama 6 Road, Bangkok 10400, Thailand.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Mahidol University, 447 Sri-Ayudhaya Road, Bangkok 10400, Thailand.
Bioinformation. 2017 Sep 30;13(9):284-292. doi: 10.6026/97320630013284. eCollection 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 groove binding ligands and thus act as potential anti-cancer agents.
从灵芝中分离出的三萜类化合物（GLTs）具有广泛的抗癌特性，包括抗增殖、抗转移和抗血管生成活性。目前的研究揭示了GLTs在诱导癌细胞凋亡和抑制端粒酶活性方面的作用，而对健康细胞的毒性要低得多。选择性结合并稳定G-四链体结构的化合物可以抑制端粒酶或下调癌基因，可能作为抗癌剂发挥作用。靶向人类端粒G-四链体DNA可能是这些GLTs发挥抗癌活性的机制之一。在本研究中，使用对接工具AutoDock4筛选了208种GLTs，以寻找具有高结合亲和力并能选择性稳定pG4DNA的配体。结果表明，灵芝酸A和灵芝酸Df表现出高结合亲和力，并选择性地结合到pG4DNA的侧沟。基于我们的发现，我们认为三萜类化合物代表了一类新的G-四链体沟结合配体，因此可作为潜在的抗癌剂。
