Chromatin & Epigenetics Lab, Department of Biotechnology, University of Kashmir, Srinagar, Jammu & Kashmir 190006, India.
Future Med Chem. 2018 Aug 1;10(16):1925-1945. doi: 10.4155/fmc-2018-0020. Epub 2018 Jul 11.
Aberrant activity of class I histone deacetylases (HDACs) has strong implications for various cancers. Targeting these HDACs with synthetic HDAC inhibitors has shown significant side effects such as atrial fibrillation and QT prolongation emphasizing the need of natural inhibitors as substitutes to synthetic ones.
The binding propensity of the two plant-derived inhibitors apigenin and luteolin towards class I HDAC isoforms was checked using extra-precision molecular docking and implicit solvation MMGBSA. Apigenin showed a superior binding affinity against these isoforms as compared to luteolin. Both inhibitors docked stable to the binding pocket of these HDACs as determined by molecular dynamics simulation study.
Apigenin and luteolin may serve as substitutes to synthetic inhibitors for effective HDAC based anticancer therapy.
I 类组蛋白去乙酰化酶（HDACs）的异常活性对各种癌症有重要影响。用合成的 HDAC 抑制剂靶向这些 HDACs 已显示出明显的副作用，如心房颤动和 QT 延长，这强调了需要天然抑制剂来替代合成抑制剂。
使用超精分子对接和隐式溶剂化 MMGBSA 检查了两种植物源性抑制剂芹菜素和木樨草素对 I 类 HDAC 同工型的结合倾向。与木樨草素相比，芹菜素对这些同工型表现出更高的结合亲和力。分子动力学模拟研究表明，这两种抑制剂都能稳定地结合到这些 HDAC 的结合口袋中。
芹菜素和木樨草素可以作为合成抑制剂的替代品，用于有效的基于 HDAC 的抗癌治疗。
