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A Rational Design, Synthesis, Biological Evaluation and Structure--Activity Relationship Study of Novel Inhibitors against Cyanobacterial Fructose-1,6-bisphosphate Aldolase.
Han, Xinya; Zhu, Xiuyun; Zhu, Shuaihua; Wei, Lin; Hong, Zongqin; Guo, Li; Chen, Haifeng; Chi, Bo; Liu, Yan; Feng, Lingling; Ren, Yanliang; Wan, Jian.
Afiliação
  • Han X; Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University , Wuhan, Hubei 430079, China.
  • Zhu X; Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University , Wuhan, Hubei 430079, China.
  • Zhu S; Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University , Wuhan, Hubei 430079, China.
  • Wei L; Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University , Wuhan, Hubei 430079, China.
  • Hong Z; Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University , Wuhan, Hubei 430079, China.
  • Guo L; Hubei Environmental Monitoring Central Station , Wuhan, Hubei 430072, China.
  • Chen H; Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University , Wuhan, Hubei 430079, China.
  • Chi B; Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University , Wuhan, Hubei 430079, China.
  • Liu Y; Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University , Wuhan, Hubei 430079, China.
  • Feng L; Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University , Wuhan, Hubei 430079, China.
  • Ren Y; Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University , Wuhan, Hubei 430079, China.
  • Wan J; Key Laboratory of Pesticide & Chemical Biology (CCNU), Ministry of Education, Department of Chemistry, Central China Normal University , Wuhan, Hubei 430079, China.
J Chem Inf Model ; 56(1): 73-81, 2016 Jan 25.
Article em En | MEDLINE | ID: mdl-26669534
In the present study, a series of novel maleimide derivatives were rationally designed and optimized, and their inhibitory activities against cyanobacteria class-II fructose-1,6-bisphosphate aldolase (Cy-FBA-II) and Synechocystis sp. PCC 6803 were further evaluated. The experimental results showed that the introduction of a bigger group (Br, Cl, CH3, or C6H3-o-F) on the pyrrole-2',5'-dione ring resulted in a decrease in the Cy-FBA-II inhibitory activity of the hit compounds. Generally, most of the hit compounds with high Cy-FBA-II inhibitory activities could also exhibit high in vivo activities against Synechocystis sp. PCC 6803. Especially, compound 10 not only shows a high Cy-FBA-II activity (IC50 = 1.7 µM) but also has the highest in vivo activity against Synechocystis sp. PCC 6803 (EC50 = 0.6 ppm). Thus, compound 10 was selected as a representative molecule, and its probable interactions with the surrounding important residues in the active site of Cy-FBA-II were elucidated by the joint use of molecular docking, molecular dynamics simulations, ONIOM calculations, and enzymatic assays to provide new insight into the binding mode of the inhibitors and Cy-FBA-II. The positive results indicate that the design strategy used in the present study is very likely to be a promising way to find novel lead compounds with high inhibitory activities against Cy-FBA-II in the future. The enzymatic and algal inhibition assays suggest that Cy-FBA-II is very likely to be a promising target for the design, synthesis, and development of novel specific algicides to solve cyanobacterial harmful algal blooms.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Desenho de Fármacos / Relação Quantitativa Estrutura-Atividade / Synechocystis / Inibidores Enzimáticos / Frutose-Bifosfato Aldolase Idioma: En Revista: J Chem Inf Model Assunto da revista: INFORMATICA MEDICA / QUIMICA Ano de publicação: 2016 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Desenho de Fármacos / Relação Quantitativa Estrutura-Atividade / Synechocystis / Inibidores Enzimáticos / Frutose-Bifosfato Aldolase Idioma: En Revista: J Chem Inf Model Assunto da revista: INFORMATICA MEDICA / QUIMICA Ano de publicação: 2016 Tipo de documento: Article País de afiliação: China