Ahmed Mahmoud S, El-Senduny Fardous, Taylor Jessica, Halaweish Fathi T
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, The British University in Egypt, El-Sherouk, Cairo, Egypt.
Department of Chemistry, Faculty of Science, Mansoura University, Mansoura, Egypt.
Chem Biol Drug Des. 2017 Sep;90(3):478-484. doi: 10.1111/cbdd.12963. Epub 2017 Apr 25.
Assembly of cucurbitacin inspired estrone analogs has been previously synthesized and screened against melanoma cell lines. Further synthetic optimization was executed via installation of Azide polar functional moiety across 23, 24 α, β-unsaturated ketone side chain using Michael addition reaction. This was followed by biological screening against melanoma cell lines employing MTT assay, in-cell-based ELISA assay, and Western blot analysis to monitor the potential of the synthesized analogs to inhibit the phosphorylated ERK levels. This resulted in evolution of MH-4 possessing IC of 3.59 μm with significant decrease in the p-ERK and targeting MAPK pathway.
葫芦素激发的雌酮类似物的组装体先前已被合成并针对黑色素瘤细胞系进行筛选。通过使用迈克尔加成反应在23、24α，β-不饱和酮侧链上安装叠氮化物极性功能部分来进行进一步的合成优化。随后，采用MTT法、基于细胞的ELISA法和蛋白质印迹分析对黑色素瘤细胞系进行生物学筛选，以监测合成类似物抑制磷酸化ERK水平的潜力。这导致了MH-4的演变，其IC为3.59μm，p-ERK显著降低并靶向MAPK途径。
