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Design, synthesis and biological evaluation of 2-(3,4-dimethoxyphenyl)-6 (1,2,3,6-tetrahydropyridin-4-yl)imidazo[1,2-a]pyridine analogues as antiproliferative agents.
Bioorganic & Medicinal Chemistry Letters ( IF 2.5 ) Pub Date : 2019-08-07 , DOI: 10.1016/j.bmcl.2019.08.013
Surendar Chitti 1 , SrinivasaRao Singireddi 1 , Pochana Santosh Kumar Reddy 1 , Prakruti Trivedi 2 , Yamini Bobde 2 , Chandan Kumar 3 , Krishnan Rangan 1 , Balaram Ghosh 2 , Kondapalli Venkata Gowri Chandra Sekhar 1
Affiliation  

Two series of forty five novel 2-(3,4-dimethoxyphenyl)-6-(1,2,3,6-tetrahydropyridin-4-yl) imidazo[1,2-a]pyridine analogues (IPA 122, IPS 122 and IP-NH) have been designed, synthesized and structures confirmed by 1H NMR, 13C NMR, mass spectrometry. Furthermore, single crystal was developed for IPS-13. All the final derived conjugates were evaluated for their in vitro antiproliferative activity against a panel of diverse cancer cell lines viz., A549 (lung cancer), HeLa (cervical cancer), B16F10 (melanoma) and found to show potent anticancer activity on the tested cell lines. Many of them showed the IC50 values in the range 2.0–20.0 µM. The most active compounds (IPA 5,6,8,9,12,16,17,19 and IPS 7,8,9,22) from IPA and IPS series were screened to determine their cytotoxicity on HEK-293 (human embryonic kidney) normal cell line and were found to be nontoxic to normal human cells. The molecular interactions of the derivatised conjugates were also supported by molecular docking simulations. These derivatives may serve as lead structures for development of novel potential anticancer drug candidates.



中文翻译:

设计,合成和生物评价2-(3,4-二甲氧基苯基)-6(1,2,3,6-四氢吡啶-4-基)咪唑并[1,2-a]吡啶类似物作为抗增殖剂。

两个系列的45新的2-(3,4-二甲氧基苯基)-6-(1,2,3,6-四氢吡啶-4-基)咪唑并[1,2]吡啶类似物(IPA 1 - 22IPS 1 - 22IP-NH)已经被设计,合成和结构确认通过1 H NMR,13 C NMR,质谱法。此外,为IPS-13开发了单晶。对所有最终衍生的缀合物进行体外评估对一组多种癌细胞系的抗增殖活性,即A549(肺癌),HeLa(宫颈癌),B16F10(黑素瘤),并在测试的细胞系上显示出有效的抗癌活性。他们中的许多人显示的IC 50值在2.0–20.0 µM的范围内。筛选了IPA和IPS系列中活性最高的化合物(IPA 5,6,8,9,12,16,17,19IPS 7,8,9,22)以确定其对HEK-293(人胚肾)的细胞毒性)正常细胞系,并被发现对正常人细胞无毒。衍生化的结合物的分子相互作用也受到分子对接模拟的支持。这些衍生物可以用作开发新型潜在抗癌药物候选物的先导结构。

更新日期:2019-08-07
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