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Hunig's base catalyzed synthesis of new 1-(2,3-dihydro-1H-inden-1-yl)-3-aryl urea/thiourea derivatives as potent antioxidants and 2HCK enzyme growth inhibitors.
Bioorganic Chemistry ( IF 4.5 ) Pub Date : 2019-12-29 , DOI: 10.1016/j.bioorg.2019.103558 Venkataramana Lachhi Reddy 1 , Vijay Kumar Reddy Avula 2 , Grigoriy V Zyryanov 3 , Swetha Vallela 4 , Jaya Shree Anireddy 4 , Visweswara Rao Pasupuleti 5 , Naga Raju Chamarthi 1
Bioorganic Chemistry ( IF 4.5 ) Pub Date : 2019-12-29 , DOI: 10.1016/j.bioorg.2019.103558 Venkataramana Lachhi Reddy 1 , Vijay Kumar Reddy Avula 2 , Grigoriy V Zyryanov 3 , Swetha Vallela 4 , Jaya Shree Anireddy 4 , Visweswara Rao Pasupuleti 5 , Naga Raju Chamarthi 1
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A series of 1-(2,3-dihydro-1H-indan-1-yl)-3-aryl urea/thiourea derivatives (4a-j) have been synthesized from the reaction of 2,3-dihydro-1H-inden-1-amine (2) with various aryl isocyanates/isothiocyanates (3a-j) by using N,N-DIPEA base (Hunig's base) catalyst in THF at reflux conditions. All of them are structurally confirmed by spectral (IR, 1H &13C NMR and MASS) and elemental analysis and screened for their in-vitro antioxidant activity against DPPH and NO free radicals and found that compounds 4b, 4i, 4h &4g are potential antioxidants. The obtained in vitro results were compared with the molecular docking, ADMET, QSAR and bioactivity study results performed for them and identified that the recorded in silico binding affinities were observed in good correlation with the in vitro antioxidant results. The Molecular docking analysis had unveiled the strong hydrogen bonding interactions of synthesized ligands with ARG 160 residue of protein tyrosine kinase (2HCK) enzyme and plays an effective role in its inhibition. Toxicology studies have assessed the potential risks of 4a-j and inferred that all of them were in the limits of potential drugs. The conformational analysis of 4a-j inferred that the urea/thiourea spacer linking 2,3-dihydro-1H-inden-1-amino and substituted aryl units has facilitated all these molecules to effectively bind with ARG 160 amino acid residue present on the α-helix of the protein tyrosine kinase (2HCK) enzyme specifically on chain A of hemopoetic cell kinase. Collectively this study has established a relationship between the antioxidant potentiality and ligands binding with ARG 160 amino acid residue of chain A of 2HCK enzyme to inhibit its growth as well as proliferation of reactive oxygen species in vivo.
中文翻译：
Hunig的碱催化合成了新的1-（2,3-二氢-1H-茚满-1-基）-3-芳基脲/硫脲衍生物，它们是有效的抗氧化剂和2HCK酶生长抑制剂。
由2，3-二氢-1H-茚满-（-）-N-的反应合成了一系列1-（2,3-二氢-1H-茚满-1-基）-3-芳基脲/硫脲衍生物（4a-j）。通过在回流条件下在THF中使用N，N-DIPEA碱（Hunig碱）催化剂，将1-胺（2）与各种芳基异氰酸酯/异硫氰酸酯（3a-j）结合使用。所有这些都通过光谱（IR，1H和13C NMR和MASS）和元素分析在结构上得到确认，并筛选了它们对DPPH和NO自由基的体外抗氧化活性，发现化合物4b，4i，4h和4g是潜在的抗氧化剂。将获得的体外结果与分子对接，ADMET，QSAR和对其进行的生物活性研究结果进行比较，并确定观察到的记录的计算机结合亲和力与体外抗氧化剂结果具有良好的相关性。分子对接分析揭示了合成的配体与蛋白酪氨酸激酶（2HCK）酶的ARG 160残基之间的强氢键相互作用，并在其抑制中起有效作用。毒理学研究评估了4a-j的潜在风险，并推断所有这些都在潜在药物的范围之内。对4a-j进行的构象分析表明，连接2,3-二氢-1H-茚满-1-氨基和取代的芳基单元的脲/硫脲间隔基已促进所有这些分子与α上存在的ARG 160氨基酸残基有效结合酪氨酸激酶（2HCK）酶的α-螺旋，特别是在造血细胞激酶A链上。
更新日期：2019-12-29
中文翻译：
Hunig的碱催化合成了新的1-（2,3-二氢-1H-茚满-1-基）-3-芳基脲/硫脲衍生物，它们是有效的抗氧化剂和2HCK酶生长抑制剂。
由2，3-二氢-1H-茚满-（-）-N-的反应合成了一系列1-（2,3-二氢-1H-茚满-1-基）-3-芳基脲/硫脲衍生物（4a-j）。通过在回流条件下在THF中使用N，N-DIPEA碱（Hunig碱）催化剂，将1-胺（2）与各种芳基异氰酸酯/异硫氰酸酯（3a-j）结合使用。所有这些都通过光谱（IR，1H和13C NMR和MASS）和元素分析在结构上得到确认，并筛选了它们对DPPH和NO自由基的体外抗氧化活性，发现化合物4b，4i，4h和4g是潜在的抗氧化剂。将获得的体外结果与分子对接，ADMET，QSAR和对其进行的生物活性研究结果进行比较，并确定观察到的记录的计算机结合亲和力与体外抗氧化剂结果具有良好的相关性。分子对接分析揭示了合成的配体与蛋白酪氨酸激酶（2HCK）酶的ARG 160残基之间的强氢键相互作用，并在其抑制中起有效作用。毒理学研究评估了4a-j的潜在风险，并推断所有这些都在潜在药物的范围之内。对4a-j进行的构象分析表明，连接2,3-二氢-1H-茚满-1-氨基和取代的芳基单元的脲/硫脲间隔基已促进所有这些分子与α上存在的ARG 160氨基酸残基有效结合酪氨酸激酶（2HCK）酶的α-螺旋，特别是在造血细胞激酶A链上。
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