Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P.R. China.
Tianjin Key Laboratory of TCM Chemistry and Analysis, Institute of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, P.R. China.
Mol Med Rep. 2021 Mar;23(3). doi: 10.3892/mmr.2021.11842. Epub 2021 Jan 26.
The adenosine monophosphate‑activated protein kinase (AMPK) is a promising target in drug development for various metabolic diseases. In the present study, the aim was to discover natural direct AMPK activators from natural sources, thus a virtual screening for direct AMPK activators was conducted by combining ligand‑based and structure‑based screening. A common‑feature pharmacophore model (HipHop1) was generated with two hydrogen bond acceptor lipid features and one hydrophobic region feature. A total of 1,235 natural products were screened using the HipHop1 hypothesis and CDOCKER protocol successively. According to the docking score, seven hit compounds were selected for AMPK activation assays. Ultimately, (‑)‑catechin (compound 522) and licochalcone A (compound 1148) exhibited the highest AMPK activation activity. These findings may contribute to the development of AMPK activators from medicinal plants.
腺苷单磷酸激活的蛋白激酶 (AMPK) 是药物开发中治疗各种代谢性疾病的一个有前途的靶点。本研究旨在从天然产物中发现天然的直接 AMPK 激活剂，因此采用基于配体和基于结构的筛选相结合的方法进行了虚拟筛选直接 AMPK 激活剂。利用两个氢键受体脂特征和一个疏水区特征生成了一个常见特征药效团模型 (HipHop1)。使用 HipHop1 假说和 CDOCKER 协议，对 1235 种天然产物进行了筛选。根据对接评分，选择了 7 种命中化合物进行 AMPK 激活测定。最终，（-）-儿茶素（化合物 522）和甘草查尔酮 A（化合物 1148）表现出最高的 AMPK 激活活性。这些发现可能有助于从药用植物中开发 AMPK 激活剂。
