Department of Pharmaceutical Chemistry, Drug Analysis and Radiopharmacy, Faculty of Pharmacy, Medical University of Lodz, Muszynskiego 1, 90-151, Lodz, Poland.
Faculty of Chemistry, University of Lodz, Tamka 12, 91-403, Lodz, Poland.
Eur J Pharmacol. 2020 Mar 15;871:172943. doi: 10.1016/j.ejphar.2020.172943. Epub 2020 Jan 21.
Pyrroles, an important class of heterocyclic compounds found in naturally occurring products, represent an interesting biologically active scaffold for drug design. Recently we have synthetized a series of five new fluorinated pyrrole derivatives for potential anticancer applications. All new compounds contain a trifluoromethyl and N-benzyl group, but they are different from each other by bearing a phenyl, ethoxycarbonyl or carboxylic moiety, with two of them possessing an additional phosphonyl function. The aim of this study was to evaluate anticancer activity of the new compounds in human lung and breast cancer cells. We found that compound 3, bearing a phosphonyl and phenyl group, was the most effective in attenuating growth of A549 and MCF-7 cells in a dose dependent manner with IC 36.5 μM ± 1.80 and 27.9 μM ± 1.68, respectively. Compound 3 inhibited cancer cell proliferation by cell cycle arrest at G1 phase as detected by flow cytometry analysis. Furthermore, compound 3 induced apoptosis of A549 cells by activation of caspase-3. Cancer cell migration rate was significantly inhibited when A549 and MCF-7 cells were cultured in the presence of the compound. These results demonstrate that a novel trifluoromethyl-functionalized phosphonopyrrole with a phenyl group might be a promising pyrrole analogue with anticancer potential.
吡咯是一类在天然产物中发现的重要杂环化合物，是药物设计中具有有趣生物活性的支架。最近，我们合成了一系列具有潜在抗癌应用的五种新型氟代吡咯衍生物。所有新化合物都含有三氟甲基和 N-苄基，但它们通过带有苯基、乙氧羰基或羧基部分而彼此不同，其中两个具有额外的膦酰基功能。本研究旨在评估新型化合物在人肺癌和乳腺癌细胞中的抗癌活性。我们发现，带有膦酰基和苯基的化合物 3 以剂量依赖的方式最有效地减弱 A549 和 MCF-7 细胞的生长，IC 36.5 μM ± 1.80 和 27.9 μM ± 1.68。化合物 3 通过流式细胞术分析检测到细胞周期停滞在 G1 期，从而抑制癌细胞增殖。此外，化合物 3 通过激活 caspase-3 诱导 A549 细胞凋亡。当 A549 和 MCF-7 细胞在化合物存在的情况下培养时，癌细胞迁移率显著受到抑制。这些结果表明，具有苯基的新型三氟甲基功能化膦酰吡咯可能是一种具有抗癌潜力的有前途的吡咯类似物。
