Synthesis, molecular docking and preliminary antileukemic activity of 4‐methoxybenzyl derivatives bearing an imidazo[2,1‐b][1,3,4]thiadiazoles,Chemistry & Biodiversity

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Synthesis, molecular docking and preliminary antileukemic activity of 4‐methoxybenzyl derivatives bearing an imidazo[2,1‐b][1,3,4]thiadiazoles
Chemistry & Biodiversity ( IF 2.3 ) Pub Date : 2021-01-07 , DOI: 10.1002/cbdv.202000800
B Choodamani _{1,

2} , Karla G Cano Hernandez ₃ , Sujeet Kumar ₁ , Ann Maria Tony ₄ , Austre Y Schiaffino Bustamante ₃ , Renato J Aguilera ₃ , Dominique Schols ₅ , C Gopi Mohan ₄ , Subhas S Karki _{1,

2}

Affiliation

In this study, we synthesized 22 compounds in a series with various substitution on imidazo[2,1- b ][1,3,4]thiadiazoles. The potential cytotoxic activity of these compounds investigated in leukemia cell lines by Differential Nuclear Staining (DNS). Our results identify two compounds 2-(4-methoxybenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl thiocyanate and 6-(4-chlorophenyl)-2-(4'-methoxybenzyl)imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehyde exhibited as the most cytotoxic effect against murine leukemia cells (L1210), human T-lymphocyte cells (CEM) and human cervix carcinoma cells (HeLa) with IC 50 values ranging between 0.79 to 1.6 μM. The results indicate that compound 2-(4-methoxybenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl thiocyanate is inducing phosphatidylserine externalization and caspase-3 activation which are both a hallmark of apoptosis. Docking studies showed that compound 2-(4-methoxybenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl thiocyanate binds within the active sites of transforming growth factor beta (TGF- β) type I receptor kinase domain by strong hydrogen binding and hydrophobic interactions.

中文翻译：

咪唑并[2,1-b][1,3,4]噻二唑类4-甲氧基苯甲基衍生物的合成、分子对接及初步抗白血病活性

在本研究中，我们合成了 22 种在咪唑并[2,1-b][1,3,4]噻二唑上进行不同取代的系列化合物。通过差异核染色 (DNS) 研究了这些化合物在白血病细胞系中的潜在细胞毒活性。我们的结果鉴定出两种化合物 2-(4-methoxybenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl thiocyanate 和6-(4-氯苯基)-2-(4'-甲氧基苯甲基)咪唑并[2,1-b][1,3,4]噻二唑-5-甲醛对小鼠白血病细胞(L1210)表现出最强的细胞毒性作用，人 T 淋巴细胞 (CEM) 和人宫颈癌细胞 (HeLa)，IC 50 值范围在 0.79 至 1.6 μM 之间。结果表明，化合物2-(4-甲氧基苄基)-6-(2-氧代-2H-苯并吡喃-3-基)咪唑并[2,1-b][1,3,4]噻二唑-5-基硫氰酸酯为诱导磷脂酰丝氨酸外化和 caspase-3 激活，这两者都是细胞凋亡的标志。对接研究表明，化合物 2-(4-methoxybenzyl)-6-(2-oxo-2H-chromen-3-yl)imidazo[2,1-b][1,3,4]thiadiazol-5-yl thiocyanate 结合通过强氢结合和疏水相互作用，位于转化生长因子β (TGF-β) I 型受体激酶结构域的活性位点内。

更新日期：2021-01-07

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