Design, Synthesis, In Silico Studies and In Vitro Anticancer Activity of 3‐(4‐Methoxyphenyl)azetidine Derivatives,ChemistrySelect

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Design, Synthesis, In Silico Studies and In Vitro Anticancer Activity of 3‐(4‐Methoxyphenyl)azetidine Derivatives
ChemistrySelect ( IF 1.9 ) Pub Date : 2020-12-01 , DOI: 10.1002/slct.202003654
Deepa R. Parmar ₁ , Rahul H. Rayani ₁ , Anand G. Vala ₁ , Rakesh V. Kusurkar ₁ , Roshani K. Manvar ₂ , Sahista N. Talukdar ₃ , Preeti ₄ , Vishwanath Zunjar ₅ , Satyanarayana Battula ₆ , Jigar Y. Soni ₁

Affiliation

A series of 3‐(4‐methoxyphenyl)azetidine analogues were synthesized and screened for their in vitro anticancer activity against nine different human cancer cell lines using the cell counting kit‐8 (CCK‐8) assay. The synthesized molecules were characterized by ¹H NMR, ¹³C NMR, LCMS and IR analysis. The toxicity, bioavailability and lipophilicity of all the synthesized compounds were predicted by using osiris and molinspiration model. Molecular docking study revealed that, compound 6‐(3‐(3‐(2‐aminopyridin‐4‐yl)‐4‐methoxyphenyl)azetidin‐1‐yl)picolinonitrile (4 A‐17) and 6‐(3‐(4‐methoxy‐3‐(2‐methoxypyridin‐4‐yl)phenyl)azetidin‐1‐yl)picolinonitrile (4 A‐19) were found to be potential inhibitor of human topoisomerase IIα. The cell viability studies exhibited promising antiproliferative activities of the novel synthesized compounds. 4 A‐17 (EC₅₀ 0.03 μM) was found to be more potent than standard Doxorubicin (EC₅₀ 0.07 μM) in U251 cancer cell lines. Similarly, 4 A‐19 showed considerable potency against four different cancer cell lines (HepG2, U251, A431, 786‐O) with EC₅₀ values ranging from 0.46 to 2.13 μM. These primary findings supported that molecule 4 A‐17 and 4 A‐19 should be subjected to further studies and lead optimization.

中文翻译：

3-（4-甲氧基苯基）氮杂环丁烷衍生物的设计，合成，计算机模拟研究和体外抗癌活性

合成了一系列3-（4-甲氧基苯基）氮杂环丁烷类似物，并使用细胞计数试剂盒-8（CCK-8）测定了其对九种不同人类癌细胞系的体外抗癌活性。合成的分子通过¹ H NMR，¹³ C NMR，LCMS和IR分析表征。利用osiris和molinspiration模型预测了所有合成化合物的毒性，生物利用度和亲脂性。分子对接研究表明，化合物6-（3-（3-（2-（2-氨基吡啶基-4-基）-4-甲氧基苯基）氮杂环丁烷-1-基）吡啶啉（4 A-17）和6-（3-（4 -甲氧基-3-（2-甲氧基吡啶-4-基）苯基）氮杂环丁烷-1-基）吡啶啉（4 A-19被发现是人拓扑异构酶IIα的潜在抑制剂。细胞活力研究显示了新型合成化合物的有希望的抗增殖活性。在U251癌细胞系中，发现4 A-17（EC ₅₀ 0.03μM）比标准的阿霉素（EC ₅₀ 0.07μM）更有效。同样，4 A-19对四种不同的癌细胞系（HepG2，U251，A431、786-O）表现出相当大的效力，EC ₅₀值范围为0.46至2.13μM。这些主要发现支持对分子4 A-17和4 A-19进行进一步研究和优化前导。

更新日期：2020-12-01

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