含哌嗪基团DPP-Ⅳ抑制剂类似物的合成及体外活性研究
Synthesis and in vitroactivity of DPP-IV inhibitor analogues containing piperazine
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摘要: 二肽基肽酶-Ⅳ（DPP-Ⅳ）抑制剂结构中含有伯胺或仲胺基团，与DPP-Ⅳ谷氨酸残基Glu205、Glu206形成氢键，被认为是抑制DPP-Ⅳ活性的重要因素。通过DPP-Ⅳ抑制剂分子对接计算研究发现，含有叔胺的DPP-Ⅳ抑制剂衍生物，通过活性氢原子也可以分别与Glu205、Glu206上羰基形成氢键。本研究设计并合成了14个含有叔胺的哌嗪双取代衍生物，其结构均经MS及1H NMR确证，测定了对DPP-Ⅳ的体外抑制活性，结果表明当被叔胺取代后，对DPP-Ⅳ抑制作用明显消失，因此伯胺和仲胺中氢原子对DPP-Ⅳ的抑制起着关键作用。
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关键词:
- 二肽基肽酶-Ⅳ抑制剂 /
- 哌嗪 /
- 分子对接 /
- 合成 /
- 体外活性
Abstract: The functional group primary or secondary amines of DPP-IV inhibitors provide critical hydrogen bonds to Glu205/Glu206 of DPP-IV and constitute the key factor for an effective inhibition of the enzyms.A docking study showed that the active hydrogen at tertiary amine of DPP-IV inhibitor could interact with the carbonyl at Glu-motif (Glu205-Glu206) of the DPP-IV enzyme.Fourteen potential DPP-IV inhibitors containing piperazine group were synthesized,and determined by MS and 1H NMR.In vitro inhibitory activity of these compounds against DPP-IV was evaluated.The assay results indicated that the inhibitory activity of the tertiary amines compounds against DPP-IV enzyme was lost.Therefore,it seems that hydrogen atoms in the primary or secondary amines of DPP-IV inhibitors may play a crucial role for the inhibition of DPP-IV enzyme.-
Keywords:
- DPP-IV inhibitor /
- piperazine /
- molecular docking /
- synthesis /
- in vitro activity
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