Department of Chemistry, National Institute of Technology, Rourkela 769008, Odisha, India.
Toxicology Laboratory, Applied Biology Department, CSIR - Indian Institute Of Chemical Technology, Hyderabad 500007, Telangana, India.
Bioorg Chem. 2019 Oct;91:103143. doi: 10.1016/j.bioorg.2019.103143. Epub 2019 Jul 22.
Coumarin-based different series of hydrazone derivatives were synthesized and evaluated for anticancer activity against four different human cancer cell lines. The activity of the compounds were compared with doxorubicin as a standard drug and all the compounds exhibited good to moderate cytotoxicity with IC values ranging from 6.07 to 60.45 µM against all the examined cancer cell lines. Based on the screening results, it was concluded that the compounds 12a and 18a were the most promising medicinal entities. In vitro tubulin polymerisation inhibition assay was performed for the compounds 12a and 18a and these two compounds displayed good potency when compared with colchicine as the standard drug. The interaction of these compounds with tubulin protein was also studied with the help of molecular docking technique using Discovery studio software. Furthermore, the molecular and ADMET properties of the compounds were computed with Osiris property software and PreADMET server. The compounds exhibited exciting in vitro and in silico results. Hence we propose that the compounds 12a and 18a could be developed as tubulin targeted potential antiproliferative agents.
合成了基于香豆素的不同系列腙衍生物，并对其进行了抗癌活性评价，以评估它们对四种不同的人癌细胞系的抑制作用。将这些化合物的活性与阿霉素（多柔比星）作为标准药物进行比较，所有化合物均表现出良好至中等的细胞毒性，IC 值范围为 6.07 至 60.45 μM，对所有检测的癌细胞系均有抑制作用。根据筛选结果，得出结论认为化合物 12a 和 18a 是最有前途的药用实体。对化合物 12a 和 18a 进行了体外微管蛋白聚合抑制试验，与标准药物秋水仙碱相比，这两种化合物显示出良好的活性。还利用 Discovery Studio 软件的分子对接技术研究了这些化合物与微管蛋白的相互作用。此外，还利用 Osiris Property 软件和 PreADMET 服务器计算了化合物的分子和 ADMET 性质。这些化合物表现出令人兴奋的体外和计算机模拟结果。因此，我们提出化合物 12a 和 18a 可以作为微管蛋白靶向的潜在抗增殖剂进行开发。
