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Novel N-(2-Methoxydibenzofuran-3-yl)-2-aryloxyacetamide Derivatives: Synthesis and Biological Investigation
Letters in Drug Design & Discovery ( IF 1.2 ) Pub Date : 2021-05-01 , DOI: 10.2174/1570180817999201110114107
Leyla Yurttaş 1 , Betül Kaya Çavuşoğlu 2 , Halide Edip Temel 3 , Gülşen Akalın Çiftçi 3
Affiliation  

Background: Dibenzofuran ring is a typical heterocyle that is found in many natural sources and its derivatives exhibit a wide scale of biological applications similar to its analog ring systems; furan and benzofuran.

Materials and Methods: Novel N-(2-methoxydibenzofuran-3-yl)-2-aryloxyacetamide derivatives (2a-l) were synthesized and evaluated for their cytotoxic activity against A549 lung cancer and NIH/3T3 mouse embryofibroblast cell lines. The inhibition percentages of cathepsin D, L, acetylcholinesterase (AChE) and butrylcholinesterase (BuChE) enzymes provoked by the compounds were also determined.

Results and Discussion: Most of the compounds exhibited significant cytotoxicity whose IC50 values were identified lower than the tested lowest concentration (<3.90 μg/mL). Compound 2i against cathepsin D and compound 2k against cathepsin L displayed the highest inhibitory activity. Regrettably, the compounds demonstrated very weak AChE and BuChE inhibition.

Conclusion: Compounds 2b, 2c, 2e, 2i and 2k exhibited the highest antiproliferative activity against A549 cell lines with selective profile. However, they did not display satisfying results on tested enzymes.



中文翻译:

新型 N-(2-Methoxydibenzofuran-3-yl)-2-aryloxyacetamide 衍生物:合成和生物学研究

背景:二苯并呋喃环是一种典型的杂环,存在于许多天然来源中,其衍生物与其模拟环系统类似,具有广泛的生物学应用;呋喃和苯并呋喃。

材料和方法:合成了新型 N-(2-甲氧基二苯并呋喃-3-基)-2-芳氧基乙酰胺衍生物 (2a-1),并评估了它们对 A549 肺癌和 NIH/3T3 小鼠胚胎成纤维细胞系的细胞毒活性。还测定了由化合物引起的组织蛋白酶 D、L、乙酰胆碱酯酶 (AChE) 和丁酰胆碱酯酶 (BuChE) 的抑制百分比。

结果和讨论:大多数化合物表现出显着的细胞毒性,其 IC 50值经鉴定低于测试的最低浓度 (<3.90 μg/mL)。针对组织蛋白酶 D 的化合物 2i 和针对组织蛋白酶 L 的化合物 2k 显示出最高的抑制活性。遗憾的是,这些化合物表现出非常弱的 AChE 和 BuChE 抑制作用。

结论:化合物2b、2c、2e、2i和2k对具有选择性特征的A549细胞系表现出最高的抗增殖活性。然而,他们在测试的酶上没有显示出令人满意的结果。

更新日期:2021-05-01
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