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Potential 2,4-dimethyl-1H-pyrrole-3-carboxamide bearing benzimidazole template: Design, synthesis, in vitro anticancer and in silico ADME study.

含有苯并咪唑模板的潜在 2,4-二甲基-1 h-吡咯-3-甲酰胺: 设计、合成、体外抗癌和计算机模拟研究。

  • 影响因子:3.88
  • DOI:10.1016/j.bioorg.2020.103660
  • 作者列表:"Rasal NK","Sonawane RB","Jagtap SV
  • 发表时间:2020-02-11
Abstract

:A new series of 2,4-dimethyl-1H-pyrrole-3-carboxamide derivatives bearing benzimidazole moiety was synthesized through a molecular hybridization approach and evaluated for in vitro anticancer activity by NCI-60 on leukemia, melanoma, lung, colon, CNS, ovarian, renal, prostate and breast cancer cell lines at a single dose (10 µM). Among all the synthesized conjugates, some derivatives showed more or less good activity even at such a small dose, while, compound 5-(1H-benzo[d]imidazol-2-yl)-N-(1-cyclohexylethyl)-2,4-dimethyl-1H-pyrrole-3-carboxamide (8f) displayed significant antiproliferative activity specifically against MDA-MB human cancer cell lines. Compound 8f showed promising activity against MDA-MB-435 cell line of melanoma (Growth inhibition: 62.46%) and MDA-MB-468 cell line of breast (Growth inhibition: 40.24%). Computational ADME study qualified its significant physicochemical, pharmacokinetic and drug-likeness properties with good predicted oral bioavailability. Thus this new hybrid molecules would be useful for further anticancer drug development.

摘要

: 通过分子杂交方法合成了一系列新的含有苯并咪唑基团的 2,4-二甲基-1 h-吡咯-3-甲酰胺衍生物,并通过 NCI-60 对白血病、黑色素瘤、肺、结肠、 CNS 、单剂量 (10 µ m) 的卵巢癌,肾癌,前列腺癌和乳腺癌细胞系。在所有合成的偶联物中,有些衍生物即使在如此小的剂量下也表现出或多或少的良好活性,而,化合物 5-(1 h-苯并 [d] imidazol-2-yl)-N-(1-环己基乙基) -2,4-二甲基-1 h-吡咯-3-甲酰胺 (8f) 对 MDA-MB 人癌细胞株表现出显著的抗增殖活性。化合物 8f 对黑色素瘤 MDA-MB-435 细胞株 (生长抑制: 62.46%) 和乳腺 MDA-MB-468 细胞株 (生长抑制: 40.24%) 显示出良好的活性。计算 ADME 研究证实了其显著的理化、药代动力学和药物相似性性质,预测的口服生物利用度良好。因此,这种新的杂化分子将有助于进一步的抗癌药物开发。

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