Qin Hua-Li, Leng Jing, Youssif Bahaa G M, Amjad Muhammad Wahab, Raja Maria Abdul Ghafoor, Hussain Muhammad Ajaz, Hussain Zahid, Kazmi Syeda Naveed, Bukhari Syed Nasir Abbas
Department of Pharmaceutical Engineering, School of Chemistry, Chemical Engineering and Life Science, Wuhan University of Technology, Wuhan, China.
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut, Egypt.
Chem Biol Drug Des. 2017 Sep;90(3):443-449. doi: 10.1111/cbdd.12964. Epub 2017 Mar 6.
The incidence of cancer can be decreased by chemoprevention using either natural or synthetic agents. Apart from synthetic compounds, numerous natural products have exhibited promising potential to inhibit carcinogenesis in vivo. In this study, α, β-unsaturated carbonyl-based anticancer compounds were used as starting materials to synthesize new oxime analogs. The findings from the antiproliferative assay using seven different human cancer cell lines provided a clear picture of structure-activity relationship. The oxime analogs namely 7a and 8a showed strong antiproliferative activity against the cell lines. The mechanistic effects of compounds on EGFR-TK kinases and tubulin polymerization and BRAF were investigated. In addition, the efficacy of compounds in reversing the efflux-mediated resistance developed by cancer cells was also studied. The compounds 5a and 6a displayed potent activity on various targets such as BRAF and EGFR-TK kinases and also exhibited strong antiproliferative activity against different cell lines hence showing potential of multifunctional anticancer agents.
使用天然或合成试剂进行化学预防可降低癌症发病率。除了合成化合物外，许多天然产物在体内抑制致癌作用方面已展现出有前景的潜力。在本研究中，以α,β-不饱和羰基类抗癌化合物为起始原料合成了新的肟类似物。使用七种不同人类癌细胞系进行的抗增殖试验结果清晰呈现了构效关系。肟类似物7a和8a对这些细胞系表现出较强的抗增殖活性。研究了这些化合物对表皮生长因子受体酪氨酸激酶（EGFR-TK激酶）、微管蛋白聚合以及BRAF的作用机制。此外，还研究了这些化合物逆转癌细胞产生的外排介导耐药性的效果。化合物5a和6a对BRAF和EGFR-TK激酶等多种靶点显示出强效活性，并且对不同细胞系也表现出较强的抗增殖活性，因此展现出多功能抗癌剂的潜力。
