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Design, synthesis and biological evaluation of peptidyl-prolyl cis-trans isomerase Pin1 inhibitors
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Kun LI1, Qun NIU2, Qi-hao XU2, Yu HAN2, Dan LIU2, Lin-xiang ZHAO2, *
Acta Pharmaceutica Sinica | 2020, 55(11) : 2679 - 2687
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Acta Pharmaceutica Sinica | 2020, 55(11): 2679-2687
• Original Articles •
Design, synthesis and biological evaluation of peptidyl-prolyl cis-trans isomerase Pin1 inhibitors
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Kun LI1, Qun NIU2, Qi-hao XU2, Yu HAN2, Dan LIU2, Lin-xiang ZHAO2, *
Affiliations
  • 1. Department of Pharmacy, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou 450003, China
  • 2. Key Laboratory of Structure-Based Drugs Design and Discovery(Shenyang Pharmaceutical University), Ministry of Education, Shenyang 110016, China
Published: 2020-11-12 doi: 10.16438/j.0513-4870.2020-1333
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Peptidyl-prolyl cis-trans isomerase Pin1 is over-expressed in prostate cancer cells and the level of expression correlates with the malignancy grade and prognosis in patients. In this work, twenty-one 2-(1H-benzimidazol-2-ylthio) acetic acid derivatives were designed and prepared with the aid of the crystal structure of Pin1 and our previous work. The chemical structures of the target compounds were confirmed by 1H NMR, 13C NMR, ESI-MS and IR. The inhibitory activity of compounds 6a-6i and 13a-13i against Pin1 were determined using a protease-coupled assay. The results indicated that twenty compounds were significantly superior to the positive control drug Juglone, and 6g, 6h and 13i exhibited the most potent Pin1 inhibitory activity, with IC50 values at the sub-micromolar level. The in vitro anti-proliferative activities of these analogs were evaluated by the MTT assay and several showed a moderate effect in human prostate cancer PC-3 cells. Molecular docking studies demonstrated that both the benzimidazole skeleton and the thioacetic acid fragment were indispensable for the compounds to interact with key residues in the catalytic domain of Pin1.

Pin1 inhibitor  /  benzimidazole  /  prostate cancer  /  molecular docking
Kun LI, Qun NIU, Qi-hao XU, Yu HAN, Dan LIU, Lin-xiang ZHAO. Design, synthesis and biological evaluation of peptidyl-prolyl cis-trans isomerase Pin1 inhibitors[J]. Acta Pharmaceutica Sinica, 2020 , 55 (11) : 2679 -2687 . DOI: 10.16438/j.0513-4870.2020-1333
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Article Info
doi: 10.16438/j.0513-4870.2020-1333
  • Receive Date：2020-08-14
  • Online Date：2026-01-23
  • Published：2020-11-12
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  • Received：2020-08-14
  • Revised：2020-09-01
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Affiliations
    1. Department of Pharmacy, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, School of Clinical Medicine, Henan University, Zhengzhou 450003, China
    2. Key Laboratory of Structure-Based Drugs Design and Discovery(Shenyang Pharmaceutical University), Ministry of Education, Shenyang 110016, China
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表12种不同金属材料的力学参数
科
Family		 属数
Number of
genus		 种数
Number of
species		 占总种数比例
Percentage of
total species (%)		 属
Genus		 种数
Number of
species		 占总种数比例
Percentage of total
species (%)
鹅膏菌科Amanitaceae 2 11 5.26 鹅膏菌属 Amanita 10 4.78
小菇科 Mycenaceae 2 12 5.74 丝盖伞属 Inocybe 5 2.39
多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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