1,2,3-三唑-尼美舒利杂化物：其作为潜在抗癌药物的设计、合成与评估。
1,2,3-Triazole-nimesulide hybrid: Their design, synthesis and evaluation as potential anticancer agents.
作者信息
Mareddy Jyoti, Suresh N, Kumar C Ganesh, Kapavarapu Ravikumar, Jayasree A, Pal Sarbani
机构信息
Department of Chemistry, MNR Degree & PG College, Kukatpally, Hyderabad 500085, India; Centre for Chemical Sciences and Technology, Institute of Science & Technology, Jawaharlal Nehru Technological University Hyderabad, Kukatpally, Hyderabad 500085, India.
Centre for Chemical Sciences and Technology, Institute of Science & Technology, Jawaharlal Nehru Technological University Hyderabad, Kukatpally, Hyderabad 500085, India.
出版信息
Bioorg Med Chem Lett. 2017 Feb 1;27(3):518-523. doi: 10.1016/j.bmcl.2016.12.030. Epub 2016 Dec 10.
A new hybrid template has been designed by integrating the structural features of nimesulide and the 1,2,3-triazole moiety in a single molecular entity at the same time eliminating the problematic nitro group of nimesulide. The template has been used for the generation of a library of molecules as potential anticancer agents. A mild and greener CuAAC approach has been used to synthesize these compounds via the reaction of 4-azido derivative of nimesulide and terminal alkynes in water. Three of these compounds showed promising growth inhibition (IC ∼6-10μM) of A549, HepG2, HeLa and DU145 cancer cell lines but no significant effects on HEK293 cell line. They also inhibited PDE4B in vitro (60-70% at 10μM) that was supported by the docking studies (PLP score 87-94) in silico.
通过将尼美舒利的结构特征与1,2,3 - 三唑部分整合在单个分子实体中，同时消除尼美舒利有问题的硝基，设计了一种新的杂化模板。该模板已用于生成作为潜在抗癌剂的分子库。采用温和且更环保的铜催化的叠氮化物-炔烃环加成（CuAAC）方法，通过尼美舒利的4 - 叠氮基衍生物与末端炔烃在水中的反应来合成这些化合物。其中三种化合物对A549、HepG2、HeLa和DU145癌细胞系显示出有前景的生长抑制作用（IC ∼6 - 10μM），但对HEK293细胞系无显著影响。它们在体外也抑制磷酸二酯酶4B（PDE4B，10μM时为60 - 70%），计算机对接研究（PLP评分87 - 94）在计算机模拟中支持了这一结果。
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