Malik M Shaheer, Ather Hissana, Asif Ansari Shaik Mohammad, Siddiqua Ayesha, Jamal Qazi Mohammad Sajid, Alharbi Ali H, Al-Rooqi Munirah M, Jassas Rabab S, Hussein Essam M, Moussa Ziad, Obaid Rami J, Ahmed Saleh A
Department of Chemistry, Faculty of Applied Sciences, Umm Al-Qura University, Makkah 21955, Saudi Arabia.
Department of Pharmaceutical Chemistry, College of Pharmacy, King Khalid University (KKU), Abha 62529, Saudi Arabia.
Pharmaceuticals (Basel). 2023 Feb 22;16(3):333. doi: 10.3390/ph16030333.
Indole-tethered chromene derivatives were synthesised in a one-pot multicomponent reaction using -alkyl-1-indole-3-carbaldehydes, 5,5-dimethylcyclohexane-1,3-dione, and malononitrile, catalysed by DBU at 60-65 °C in a short reaction time. The benefits of the methodology include non-toxicity, an uncomplicated set-up procedure, a faster reaction time, and high yields. Moreover, the anticancer properties of the synthesised compounds were tested against selected cancer cell lines. The derivatives and displayed very good cytotoxic activity, with IC values ranging from 7.9 to 9.1 µM. Molecular docking revealed the potent derivatives have good binding affinity towards tubulin protein, better than the control, and the molecular dynamic simulations further demonstrated the stability of ligand-receptor interactions. Moreover, the derivatives followed all the drug-likeness filters.
吲哚连接的色烯衍生物是在一锅多组分反应中合成的，该反应使用 -烷基-1-吲哚-3-甲醛、5,5-二甲基环己烷-1,3-二酮和丙二腈，在60-65°C下由DBU催化，反应时间短。该方法的优点包括无毒、设置程序简单、反应时间短和产率高。此外，还对合成化合物的抗癌特性进行了针对选定癌细胞系的测试。衍生物 和 表现出非常好的细胞毒性活性，IC值范围为7.9至9.1 μM。分子对接显示，有效的衍生物对微管蛋白具有良好的结合亲和力，优于对照，分子动力学模拟进一步证明了配体-受体相互作用的稳定性。此外，这些衍生物符合所有类药筛选标准。
