Design Synthesis and Biological Evaluation of Novel Peptide-Like Analogues as Selective COX-2 Inhibitors

机译：新型肽类似物作为选择性COX-2抑制剂的设计合成和生物学评估

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A new series of peptide-like derivatives containing different aromatic amino acids and possessing pharmacophores of COX-2 inhibitors as SO2Me or N3 attached to the para position of an end phenyl ring was synthesized for evaluation as selective cyclooxygenase-2 (COX-2) inhibitors. The synthetic reactions were based on the solid phase peptide synthesis method using Wang resin. One of the analogues, i.e., compound 2d, as the representative of these series was recognized as the most effective and the highest selective COX-2 inhibitor with IC50 value of 0.08 μM and COX-2 selectivity index of 351.2, among the other synthesized compounds. Molecular docking study was operated to determine possible binding models of compound 2d to COX-2 enzyme. The study showed that the p-azido-phenyl fragment of 2d occupied inside the secondary COX-2 binding site (Arg⁵¹³, and His⁹⁰). The structure-activity relationships acquired disclosed that compound 2d with 4-(azido phenyl) group as pharmacophore and histidine as amino acid gives the essential geometry to provide inhibition of the COX-2 enzyme with high selectivity. Compound 2d can be a good candidate for the development of new hits of COX-2 inhibitors.

机译：合成了一系列新的肽样衍生物，其包含不同的芳香族氨基酸，并具有连接到末端苯环对位的COX-2抑制剂如SO2Me或N3的药效团，以作为选择性环氧化酶2（COX-2）抑制剂进行评估。合成反应基于使用王氏树脂的固相肽合成方法。在其他合成的化合物中，其中一个类似物（即化合物2d）被认为是最有效和最具选择性的COX-2抑制剂，IC50值为0.08μM，COX-2选择性指数为351.2。。进行分子对接研究以确定化合物2d与COX-2酶的可能结合模型。研究表明，2d的对叠氮基苯基片段占据了COX-2二级结合位点（Arg ^{513 和His ^{90 ）。获得的结构-活性关系揭示了具有4-（叠氮基苯基）基团作为药效团和组氨酸作为氨基酸的化合物2d给出了必需的几何形状，以高选择性提供了对COX-2酶的抑制作用。化合物2d可能是开发COX-2抑制剂新产品的良好选择。}}

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期刊名称 Iranian Journal of Pharmaceutical Research : IJPR
作者
Mohammad Ali Ahmaditaba; Mohammad Hassan Houshdar Tehrani; Afshin Zarghi; Sorayya Shahosseini; Bahram Daraei;
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作者单位

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年(卷),期 2018(17),1
年度 2018
页码 87–92
总页数 6
原文格式 PDF
正文语种
中图分类药学;
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专利

1. Design, Synthesis, and Biological Evaluation of New Peptide Analogues as Selective COX-2 Inhibitors [J] . Ahmaditaba Mohammad A., Shahosseini Soraya, Daraei Bahram, Archiv der Pharmazie . 2017,第10期

机译：新肽类似物作为选择性COX-2抑制剂的设计，合成和生物学评估
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4. A highly selective cell permeable peptide inhibitor of proprotein convertase 1:design,synthesis and biological evaluation in cellular PC1-mediated proteolysis [C] . Ajoy Basak, Peter Koch, Marcel Dupelle, the International Peptide Symposium . 2001

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机译：新型二芳基杂环类似物的设计，合成，分子建模和生物学评价作为潜在的选择性环氧合酶-2（COX-2）抑制剂

Design Synthesis and Biological Evaluation of Novel Peptide-Like Analogues as Selective COX-2 Inhibitors

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