New quinoxaline-piperazine-oxazole conjugates: Synthesis, in vitro anticancer, in silico ADMET, and molecular docking studies,Journal of Heterocyclic Chemistry

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New quinoxaline-piperazine-oxazole conjugates: Synthesis, in vitro anticancer, in silico ADMET, and molecular docking studies
Journal of Heterocyclic Chemistry ( IF 2.0 ) Pub Date : 2024-02-05 , DOI: 10.1002/jhet.4782
Mohammad Ferazoddin ₁ , Siddhartha Marupati ₂ , Gouthami Dasari ₁ , Arshiya Banu Syeda ₁ , Mohammad Imtiyaz Ali ₁ , Ravinder Manchal ₁ , Karthik Bokkala ₃ , Srinivas Bandari ₁

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In this paper, we describe the synthesis of some new quinoxaline-piperazine-oxazole amide conjugates 6a-n from 3-chloroquinoxaline-2-carbonitrile using well-known reaction sequences. The synthesized compounds were characterized by ¹H NMR,¹³C NMR, and mass spectral analysis. The compounds were tested for their in vitro antiproliferative activity toward four different cancer cell lines such as PC-3, MCF-7, DU-145, and A-549 by MTT method. The compounds, 6c, 6h, 6i, and 6n were found to be more potent than the standard Erlotinib. In vitro tyrosine kinase EGFR inhibition studies using four potent compounds revealed that 6n has double inhibiting tendency with value IC₅₀ of 0.22 μM and 6h with value of IC₅₀ 0.27 μM compared to reference compound. Molecular docking studies of active compounds, 6c, 6h, 6i, and 6n on EGFR receptor suggested that all the compounds have more binding energies than that of Erlotinib. Furthermore, the in silico pharmacokinetic profile was accomplished for the active compounds, 6c, 6h, 6i, and 6n using SWISS/ADME and pk CSM, whereas compounds, 6h, 6i, and 6c followed Lipinski rule, Veber rule, Egan rule and Muegge rule. The remaining compound 6n did not follow Lipinski rule, Ghose rule because one common violation, that is, because of high molecular weight (MW > 350).

中文翻译：

新型喹喔啉-哌嗪-恶唑缀合物：合成、体外抗癌、计算机 ADMET 和分子对接研究

在本文中，我们描述了使用众所周知的反应顺序从 3-氯喹喔啉-2-甲腈合成一些新的喹喔啉-哌嗪-恶唑酰胺缀合物6a-n 。合成的化合物通过¹ H NMR、¹³ C NMR和质谱分析进行了表征。采用MTT法测试了化合物对PC-3、MCF-7、DU-145和A-549等四种不同癌细胞系的体外抗增殖活性。发现化合物6c、6h、6i和6n比标准厄洛替尼更有效。使用四种有效化合物进行的体外酪氨酸激酶 EGFR 抑制研究表明，与参考化合物相比，6n具有双重抑制趋势，IC ₅₀值为0.22 μM，6h的 IC ₅₀值为0.27 μM。活性化合物6c、6h、6i和6n对EGFR受体的分子对接研究表明，所有化合物都比厄洛替尼具有更高的结合能。此外，使用 SWISS/ADME 和 pk CSM完成活性化合物6c、6h、6i和6n 的计算机药代动力学特征，而化合物6h、6i和6c遵循 Lipinski 规则、 Veber 规则、 Egan 规则和 Muegge规则。剩下的化合物6n不遵循Lipinski规则，Ghose规则，因为一个常见的违反，即因为高分子量（MW>350）。

更新日期：2024-02-05

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