Napiórkowska Mariola, Grosicka-Maciąg Emilia, Podsadni Piotr, Otto-Ślusarczyk Dagmara
Chair and Department of Biochemistry, Medical University of Warsaw, 1 Banacha Str., 02-097 Warsaw, Poland.
Department of Biochemistry and Laboratory Diagnostic, Collegium Medicum, Cardinal Stefan Wyszyński University, Kazimierza Wóycickiego 1 Str., 01-938 Warsaw, Poland.
Int J Mol Sci. 2025 Jun 8;26(12):5493. doi: 10.3390/ijms26125493.
The presented results are a continuation of our research on the synthesis and biological properties of halogen benzofuran derivatives, particularly their anticancer potential. We examined the cytotoxicity of two derivatives, methyl 4-chloro-6-(dichloroacetyl)-5-hydroxy-2-methyl-1-benzofuran-3-carboxylate () and methyl 6-(dibromoacetyl)-5-methoxy-2-methyl-1-benzofuran-3-carboxylate (), in the following human cancer cell lines: SW480, SW620, HCT116, HepG2, PC3, A549, and MDA. The MTT assay results showed that compound exhibited the most promising activity against A549 cells, while compound demonstrated significant activity against both A549 cells and HepG2 cells. The biological activity of these compounds was evaluated by the trypan blue assay, reactive oxygen species generation, lipid peroxidation and IL-6 secretion. To investigate the proapoptotic activity of these compounds, the two following types of tests were performed: Annexin V Apoptosis Detection Kit I and Caspase-Glo 3/7 assay. Moreover, we checked the effect of both tested derivatives on the cell cycle and tubulin polymerization. The obtained results revealed that the presence of bromine and methoxy group in the structure has an influence on the biological properties of compound . This derivative exhibited stronger pro-oxidative effects and proapoptotic properties compared to those observed for derivative . Both compounds decreased IL 6 secretion in the tested cancer cell lines; however, the stronger effect was observed for HepG2 cells. Analysis of the cell cycle in the presence of the tested compounds revealed that compound induced G2/M phase arrest in HepG2 cells, while compound caused cell cycle arrest at the S and G2/M phases in A549 cells. On the other hand, both derivatives had a minimal effect on tubulin polymerization. These findings suggest that compounds and could serve as starting points for further development of anticancer agents.
所呈现的结果是我们对卤代苯并呋喃衍生物的合成及生物学特性，尤其是其抗癌潜力研究的延续。我们检测了两种衍生物，4-氯-6-(二氯乙酰基)-5-羟基-2-甲基-1-苯并呋喃-3-羧酸甲酯（）和6-(二溴乙酰基)-5-甲氧基-2-甲基-1-苯并呋喃-3-羧酸甲酯（）在以下人类癌细胞系中的细胞毒性：SW480、SW620、HCT116、HepG2、PC3、A549和MDA。MTT法检测结果表明，化合物对A549细胞表现出最有前景的活性，而化合物对A549细胞和HepG2细胞均表现出显著活性。通过台盼蓝检测、活性氧生成、脂质过氧化和IL-6分泌来评估这些化合物的生物学活性。为了研究这些化合物的促凋亡活性，进行了以下两种类型的试验：膜联蛋白V凋亡检测试剂盒I和Caspase-Glo 3/7检测。此外，我们检查了两种受试衍生物对细胞周期和微管蛋白聚合的影响。所得结果表明，结构中溴和甲氧基的存在对化合物的生物学特性有影响。与衍生物相比，该衍生物表现出更强的促氧化作用和促凋亡特性。两种化合物均降低了受试癌细胞系中IL-6的分泌；然而，在HepG2细胞中观察到更强的效果。在受试化合物存在的情况下对细胞周期进行分析表明，化合物在HepG2细胞中诱导G2/M期阻滞，而化合物在A549细胞中导致细胞周期在S期和G2/M期阻滞。另一方面，两种衍生物对微管蛋白聚合的影响极小。这些发现表明，化合物和可作为进一步开发抗癌药物的起点。
