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首页> 外文期刊>RSC Advances >Novel indole based hybrid oxadiazole scaffolds with N-(substituted-phenyl)butanamides: synthesis, lineweaver-burk plot evaluation and binding analysis of potent urease inhibitors
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Novel indole based hybrid oxadiazole scaffolds with N-(substituted-phenyl)butanamides: synthesis, lineweaver-burk plot evaluation and binding analysis of potent urease inhibitors

机译：基于新型吲哚的杂交氧基唑支架，用N-（取代苯基）丁烷烃：合成，Lineweaver-Burk绘图评估和有效脲酶抑制剂的结合分析

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摘要

In the study presented herein, 4-(1H-indol-3-yl) butanoic acid (1) was sequentially transformed in the first phase into ethyl 4-(1H-indol-3-yl) butanoate (2), 4-(1H-indol-3-yl) butanohydrazide (3) and 5-[3-(1H-indol-3-yl) propyl]-1,3,4- oxadiazole-2-thiol (4) as a nucleophile. In the second phase, various electrophiles were synthesized by reacting substituted-anilines, 5a-j, with 4-chlorobutanoyl chloride (6) to afford 4-chloro-N-(substituted-phenyl) butanamides (7a-j). In the final phase, nucleophilic substitution reaction of 4 was carried out with different electrophiles, 7a-j, to achieve novel indole based oxadiazole scaffolds with N-(substituted-phenyl) butamides (8a-j). The structural confirmation of all the as-synthesized compounds was performed by spectral and elemental analysis. These molecules were screened for their in vitro inhibitory potential against urease enzyme and were found to be potent inhibitors. The results of enzyme inhibitory kinetics showed that compound 8c inhibited the enzyme competitively with a K-i value 0.003 mu M. The results of the in silico study of these scaffolds were in full agreement with the experimental data and the ligands showed good binding energy values. The hemolytic study revealed their mild cytotoxicity towards cell membranes and hence, these molecules can be regarded as valuable therapeutic agents in drug designing programs.
机译：在研究本文中所呈现，4-（1H-吲哚-3-基）丁酸（1）在第一阶段进入乙基依次转化4-（1H-吲哚-3-基）丁酸甲酯（2），4-（ 1H-吲哚-3-基）丁酰肼（3）和5- [3-（1H-吲哚-3-基）丙基] -1,3,4-二唑-2-硫醇（4）作为亲核试剂。在第二阶段中，通过使取代的 - 苯胺，5a-j，用4-氯丁二醇酰氯（6）反应合成各种电泳，得到4-氯-N-（取代 - 苯基）丁烷酰胺（7a-j）。在最终阶段，用不同的电泳，7a-j进行4的亲核取代反应，以实现具有N-（取代 - 苯基）丁酰胺（8a-j）的新型吲哚基的恶二唑支架。通过光谱和元素分析进行​​所有和合成化合物的结构确认。将这些分子筛选用于其对脲酶的体外抑制潜力，并被发现是有效的抑制剂。酶抑制动力学的结果表明，化合物8C竞争性地抑制酶的K-I值0.003μm。这些支架的硅研究的结果与实验数据完全一致，配体显示出良好的结合能值。溶血研究揭示了它们对细胞膜的轻度细胞毒性，因此，这些分子可以被视为药物设计方案中的有价值的治疗剂。

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  • 来源
    《RSC Advances》 |2018年第46期|共12页
  • 作者

    Nazir Majid; Abbasi Muhammad Athar; Aziz-ur-Rehman; Siddiqui Sabahat Zahra; Raza Hussain; Hassan Mubashir; Shah Syed Adnan Ali; Shahid Muhammad; Seo Sung-Yum;

  • 作者单位

    Govt Coll Univ Dept Chem Lahore 54000 Pakistan;

    Govt Coll Univ Dept Chem Lahore 54000 Pakistan;

    Govt Coll Univ Dept Chem Lahore 54000 Pakistan;

    Govt Coll Univ Dept Chem Lahore 54000 Pakistan;

    Kongju Natl Univ Dept Biol Sci Coll Nat Sci Gongju 32588 South Korea;

    Kongju Natl Univ Dept Biol Sci Coll Nat Sci Gongju 32588 South Korea;

    Univ Teknol MARA Atta ur Rahman Inst Nat Prod Discovery AuRIns Fac Pharm Level 9 FF3 Puncak Alam Campus Bandar Puncak Alam 42300 Selangor Darul Malaysia;

    Univ Agr Faisalabad Dept Biochem Faisalabad 38040 Pakistan;

    Kongju Natl Univ Dept Biol Sci Coll Nat Sci Gongju 32588 South Korea;

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