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新型 N'-((4-氧代-4H-色烯-3-基)亚甲基)苯甲酰肼的设计与合成作为蓝细菌果糖-1,6-/景天庚酮糖-1,7-二磷酸酶抑制剂。

Design and syntheses of novel N'-((4-oxo-4H-chromen-3-yl)methylene)benzohydrazide as inhibitors of cyanobacterial fructose-1,6-/sedoheptulose-1,7-bisphosphatase.

机构信息

Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Wuhan 430079, China.

出版信息

Bioorg Med Chem. 2013 Jun 1;21(11):2826-31. doi: 10.1016/j.bmc.2013.04.003. Epub 2013 Apr 15.

Abstract

Cyanobacterial fructose-1,6-/sedoheptulose-1,7-bisphoshatase (Cy-FBP/SBPase) is an important target enzyme for finding inhibitors to solve harmful algal bloom (HAB). In this study, as potential inhibitors of Cy-FBP/SBPase, a series of novel chromone-connecting benzohydrazone compounds (Novel N'-((4-oxo-4H-chromen-3-yl)methylene)benzohydrazide) were designed and synthesized. Their inhibitory activities against Cy-FBP/SBPase were further examined in vitro. Some of these compounds, such as f6-f8, f11, f12 and f16, exhibit higher inhibitory activities (IC50=11.2-16.1 μM), especially, the compound f7 was identified as the most potent inhibitor with IC50 value of 11.2 μM. The probable binding-mode of compound f7 was further analyzed carefully by molecular docking methods. These results indicate that compound f7 could be used as a lead compound for further optimization and might have potential to be developed as a new algicide.

摘要

蓝细菌果糖-1,6-/景天庚酮糖-1,7-双磷酸酶 (Cy-FBP/SBPase) 是寻找抑制剂以解决有害藻华 (HAB) 的重要靶标酶。在这项研究中,作为 Cy-FBP/SBPase 的潜在抑制剂,设计并合成了一系列新型色酮连接苯甲酰腙化合物 (新型 N'-((4-氧代-4H-色烯-3-基)亚甲基)苯甲酰肼)。进一步在体外检测了它们对 Cy-FBP/SBPase 的抑制活性。其中一些化合物,如 f6-f8、f11、f12 和 f16,表现出更高的抑制活性 (IC50=11.2-16.1 μM),特别是化合物 f7 被鉴定为最有效的抑制剂,IC50 值为 11.2 μM。通过分子对接方法进一步仔细分析了化合物 f7 的可能结合模式。这些结果表明,化合物 f7 可用作进一步优化的先导化合物,并且可能有潜力开发为新型杀藻剂。

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