Faculty of Pharmaceutical Sciences, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Division of Natural Drug Discovery, Institute of Natural Medicine, University of Toyama, 2630 Sugitani, Toyama 930-0194, Japan.
Bioorg Med Chem Lett. 2020 Apr 1;30(7):126964. doi: 10.1016/j.bmcl.2020.126964. Epub 2020 Jan 11.
E- and Z-guggulsterones and nine guggulsterone derivatives (GSDs) were synthesized and evaluated for their preferential cytotoxicity against human PANC-1 cell in nutrient deprived medium utilizing antiausterity strategy. Among the synthesized compounds, GSD-1 and GSD-7 showed potent cytotoxicity against PANC-1 cells under nutrient-deprived conditions in a concentration dependent manner, with a PC value of 1.6 μM and 3.2 μM, respectively. The effect of GSD-1 and GSD-7 was further evaluated in a real time using live cell imaging. Both of these compounds altered PANC-1 cell morphology, leading to cell death at sub micromolar concentration range. GSD-1 and GSD-7 also inhibited PANC-1 cell colony formation in a concentration-dependent manner. GSD-1 and GSD-7 are lead structure for the anti-austerity drug development.
E- 和 Z- 芝麻素和 9 种芝麻素衍生物（GSD）被合成，并利用抗饥饿策略，在营养缺乏的培养基中评价它们对人 PANC-1 细胞的选择性细胞毒性。在合成的化合物中，GSD-1 和 GSD-7 在营养缺乏条件下以浓度依赖的方式对 PANC-1 细胞表现出很强的细胞毒性，其 PC 值分别为 1.6 μM 和 3.2 μM。使用实时细胞成像进一步评估了 GSD-1 和 GSD-7 的作用。这两种化合物都改变了 PANC-1 细胞的形态，导致在亚微米浓度范围内细胞死亡。GSD-1 和 GSD-7 还以浓度依赖的方式抑制 PANC-1 细胞集落形成。GSD-1 和 GSD-7 是抗饥饿药物开发的先导结构。
