新型抗白血病癌症药物1,2,3,4-四嗪的设计与合成。

Oznur Eyilcim, Fulya Gunay, Omer Tahir Gunkara, Yuk Yin Ng, Ozlem Ulucan, Ihsan Erden
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引用次数: 0

摘要

设计合成了一系列新的1,2,3,4-四嗪类化合物。用1H-NMR谱、13CNMR谱和HRMS测定了这些新化合物的结构。计算方法表明,DHFR是新合成的11个化合物的假定靶标。广泛的分子动力学模拟和分子对接模拟被用来评估DHFR作为一种潜在的靶蛋白。通过体外MTT试验评估了化合物对五种不同类型的白血病细胞系(Jurkat、Nalm-6、Reh、K562和Molt-4)和一种非白血病细胞株(Hek293T)的抗癌活性,并使用伊马替尼作为对照药物。在这些化合物中,3a对除Reh细胞系外的所有白血病细胞系表现出最好的活性。对于Nalm-6、K562、Jurkat和Molt-4细胞系,发现IC50值分别为15.98、19.12、23.15和25.80 μM。我们的工作重点是合成原始和新的1,2,3,4-四嗪衍生物,同时为发现更有效的新抗白血病药物做出贡献。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Design and synthesis of novel 1,2,3,4-tetrazines as new anti-leukemia cancer agents

Design and synthesis of novel 1,2,3,4-tetrazines as new anti-leukemia cancer agents

A series of novel 1,2,3,4-tetrazines were designed and synthesized. 1H-NMR spectroscopy, 13C NMR spectroscopy, and HRMS were used to determine the structures of this novel compounds. Computational approaches suggested that DHFR is a putative target for the newly synthesized 11 compounds. Extensive molecular dynamics simulations followed by molecular docking simulations were employed to evaluate DHFR as a potential target protein. The anticancer activities of the compounds were evaluated against five different types of leukemia cell lines (Jurkat, Nalm-6, Reh, K562, and Molt-4) and one non-leukemic cell line (Hek293T) by MTT test in vitro and imatinib was used as a control drug. Among these compounds, 3a exhibited the best activity against all the leukemic cell lines, except Reh cell line. For Nalm-6, K562, Jurkat, and Molt-4 cell lines, IC50 values were found to be 15.98, 19.12, 23.15, and 25.80 μM, respectively. Our work focuses on the synthesis of original and novel 1,2,3,4-tetrazine derivatives while contributing to the ongoing effort to discover more potent new antileukemia agents.

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