新型胡椒碱-脒基混合化合物：通过多靶点抑制途径设计、合成及抗增殖活性。
Novel piperine-carboximidamide hybrids: design, synthesis, and antiproliferative activity via a multi-targeted inhibitory pathway.
机构信息
Department of Chemistry, College of Sciences, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
出版信息
J Enzyme Inhib Med Chem. 2023 Dec;38(1):376-386. doi: 10.1080/14756366.2022.2151593.
A new series of piperine-carboximidamide hybrids VIa-k was developed as a new cytotoxic agent targeting EGFR, BRAF, and CDK2. The antiproliferative effect against four cancer cells was investigated against erlotinib. Hybrids , , , , and have the highest antiproliferative activity. Compounds , , , , and inhibited EGFR with IC values ranging from 96 to 127 nM. Compounds and had the most potent inhibitory activity as BRAF (IC = 49 and 40 nM, respectively) and were discovered to be potent inhibitors of cancer cell proliferation (GI = 44 and 35 nM against four cancer cell lines, respectively). Compound , the most effective derivative as an antiproliferative agent, demonstrated potent anti-CDK2 action with an IC value of 12 nM, which is 1.5-fold more potent than the reference dinaciclib. Finally, , , and have a high capacity to inhibit LOX-IMVI cell line survival.
开发了一系列新的胡椒碱-脒基杂合体 VIa-k，作为针对 EGFR、BRAF 和 CDK2 的新型细胞毒性药物。针对厄洛替尼，研究了对四种癌细胞的增殖抑制作用。杂种 、 、 、 和 具有最高的增殖抑制活性。化合物 、 、 、 和 对 EGFR 的抑制作用的 IC 值范围为 96 至 127 nM。化合物 和 对 BRAF 具有最强的抑制活性（IC = 49 和 40 nM），并被发现是癌细胞增殖的有效抑制剂（对四种癌细胞系的 GI = 44 和 35 nM）。作为增殖抑制剂最有效的衍生物 ，对 CDK2 具有很强的抑制作用，IC 值为 12 nM，比对照药 dinaciclib 强 1.5 倍。最后， 、 、 和 对 LOX-IMVI 细胞系的存活具有很强的抑制能力。
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