Hasanpour Zahra, Salehi Peyman, Bararjanian Morteza, Esmaeili Mohammad-Ali, Alilou Mostafa, Mohebbi Maryam
Department of Phytochemistry, Medicinal Plants and Drugs Research Institute, Shahid Beheshti University, Tehran, Iran.
Schulich School of Medicine and Dentistry and Robarts Research Institute, Western University, London, Ontario, Canada.
Iran J Pharm Res. 2021 Spring;20(2):546-560. doi: 10.22037/ijpr.2020.113213.14170.
Novel 1,2,3-triazole-tethered 9-bromonoscapine derivatives were synthesized by the propargylation of N-nornoscapine followed by Huisgen's 1,3-dipolar cycloaddition of the terminal alkynes with different azides. Cytotoxicity of the products was studied by MTT assay against the MCF-7 breast cancer cell line. Most of the compounds revealed a better cytotoxicity than N-nornoscapine and 9-bromonornoscapine as the parent compounds. Among the synthesized compounds, those with a hydroxylated aliphatic side chain (5p, 5q, and 5r) showed the highest activities (IC50s: 47.2, 37.9, and 32.3 μg/mL, respectively). Molecular docking studies showed that these compounds also had the highest docking scores and effective interactions with binding sites equal to -8.074, -7.425 and -7.820 kcal/mol, respectively.
通过去甲石蒜碱的炔丙基化反应，然后使末端炔烃与不同叠氮化物进行惠斯根1,3 -偶极环加成反应，合成了新型的1,2,3 -三唑连接的9 -溴石蒜碱衍生物。通过MTT法研究了产物对MCF - 7乳腺癌细胞系的细胞毒性。大多数化合物显示出比作为母体化合物的去甲石蒜碱和9 -溴去甲石蒜碱更好的细胞毒性。在合成的化合物中，具有羟基化脂肪族侧链的化合物（5p、5q和5r）表现出最高活性（IC50分别为47.2、37.9和32.3 μg/mL）。分子对接研究表明，这些化合物也具有最高的对接分数，并且与结合位点的有效相互作用分别为-8.074、-7.425和-7.820 kcal/mol。
