Design and Synthesis of Novel Imidazole Derivatives Possessing Triazole Pharmacophore with Potent Anticancer Activity, and In Silico ADMET with GSK-3β Molecular Docking Investigations

International Journal of Molecular Sciences

Fawzia Al-blewi¹  Arshi Naqvi¹  MohamedReda Aouad¹  Faizah Aljohani¹  Nadjet Rezki¹  SalmaAkram Shaikh¹  Saleh Ihmaid² 

[1] Department of Chemistry, College of Science, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi Arabia;Pharmacognosy and Pharmaceutical Chemistry Department, College of Pharmacy, Taibah University, Al-Madinah Al-Munawarah 30002, Saudi Arabia;

关键词: 1,2,3-triazole;    imidazole;    click synthesis;    anticancer activity;    docking study;   

DOI  :  10.3390/ijms22031162

来源: DOAJ

【 摘 要 】

A library of novel imidazole-1,2,3-triazole hybrids were designed and synthesized based on the hybrid pharmacophore approach. Therefore, copper(I)catalyzed click reaction of thiopropargylated-imidazole 2 with several organoazides yielded two sets of imidazole-1,2,3-triazole hybrids carrying different un/functionalized alkyl/aryl side chains 4a–k and 6a–e. After full spectroscopic characterization using different spectral techniques (IR, ¹H, ¹³C NMR) and elemental analyses, the resulted adducts were screened for their anticancer activity against four cancer cell lines (Caco-2, HCT-116, HeLa, and MCF-7) by the MTT assay and showed significant activity. In-silico molecular docking study was also investigated on one of the prominent cancer target receptors, i.e., glycogen synthase kinase-3β (GSK-3β), revealing a good binding interaction with our potent compound, 4k and was in agreement with the in vitro cytotoxic results. In addition, the ADMET profile was assessed for these novel derivatives to get an insight on their pharmacokinetic/dynamic attributes. Finally, this research design and synthesis offered click chemistry products with interesting biological motifs mainly 1,2,3 triazoles linked to phenyl imidazole as promising candidates for further investigation as anticancer drugs.

【 授权许可】

Unknown