Faculty of Health Science, Federal University of Grande Dourados - UFGD, Dourados, Mato Grosso do Sul State, Brazi.
Industrial chemistry course, State University of Mato Grosso do Sul - UEMS, Dourados, Mato Grosso do Sul State, Brazil.
Curr Pharm Biotechnol. 2022;23(13):1623-1633. doi: 10.2174/1389201023666211217150837.
Appropriate substituents in the galloyl group could lead to significant biological properties.
Novel galloyl-substituted compounds bearing 2-substituted-1, 3, 4-oxadiazol-5-yl, 5- substituted-1,2,4-triazol-3-yl, and carboxamide groups were synthesized and evaluated for their antiproliferative activity. Additionally, galloyl hydrazide (2) was evaluated by performing cytotoxicity, membrane integrity, cell cycle, and apoptosis assays in HepG2/C3A cells.
General procedure was used for the synthesis of galloyl-substituted (3-9, 11) and characterized by their spectroscopic data (1H and 13C NMR). The antiproliferative activity of all novel galloyl derivatives was evaluated against nine human tumors and one nontumoral cell line. Three response parameters (GI50, TGI, and LC50) were calculated. The cytotoxicity test was performed for the resazurin assay. The membrane integrity, cell cycle, and apoptosis assays were performed by flow cytometry.
The substitution of the methoxy group of the galloyl ring system for a carboxamide group (3, 4, 5, and 6) produced compounds with moderate antitumoral activity, particularly 6, against six human cancer cell lines, K-562, PC-3, NCI-ADR/RES, OVCAR, 786-0 and NCI-H460, with GI50 values ≤ 9.45 μg/mL. Triazole derivatives 7 and 8 exhibited higher antitumoral activity toward OVCAR, MCF-7 and leukemia K-562 cell lines, exhibiting GI50 values less than 10 μg/mL. Compound 11 displayed significant activity against PC-3 (GI50 = 4.31 μg/mL), OVCAR (GI50 = 8.84 μg/mL) and K-562 (GI50 = 8.80 μg/mL) cell lines. Galloyl hydrazide (2) had cytotoxic activity in HepG2/C3A cells (IC50 = 153.7 μg/mL). In membrane permeability, cell count, cell cycle, and apoptosis assays, as determined using the IC50 of compound (2) in HepG2/C3A cells, increased membrane permeability, decreased cell count, altered cell cycle, and initial apoptosis was observed compared to the control group.
Thus, our results showed for the first time the synthesis, antiproliferative activity, and cytotoxicity of galloyl-substituted compounds. Galloyl-substitution does not have a very strong synergistic effect in the inhibition of cancer cell proliferation compared with galloyl hydrazide (2). Compound 2 demonstrated promising activity in HepG2/C3A hepatocarcinoma cells.
在没食子酰基上引入合适的取代基可能会带来显著的生物学特性。
合成了具有 2-取代-1,3,4-噁二唑-5-基、5-取代-1,2,4-三唑-3-基和羧酰胺基的新型没食子酰取代化合物，并评价其抗增殖活性。此外，还通过在 HepG2/C3A 细胞中进行细胞毒性、膜完整性、细胞周期和细胞凋亡测定，评估了没食子酰腙（2）的活性。
采用通用方法合成了没食子酰取代的（3-9,11）化合物，并通过其光谱数据（1H 和 13C NMR）进行了表征。所有新型没食子酰衍生物的抗增殖活性均采用 9 个人类肿瘤细胞株和 1 个非肿瘤细胞株进行了评价。计算了 3 个反应参数（GI50、TGI 和 LC50）。细胞毒性试验采用 Resazurin 法进行。通过流式细胞术进行了膜完整性、细胞周期和细胞凋亡测定。
没食子酰环系统中甲氧基被羧酰胺基取代（3、4、5 和 6）产生了具有中等抗肿瘤活性的化合物，特别是化合物 6，对 6 个人类癌细胞系，包括 K-562、PC-3、NCI-ADR/RES、OVCAR、786-0 和 NCI-H460，表现出中等抗肿瘤活性，GI50 值均≤9.45μg/mL。三唑衍生物 7 和 8 对 OVCAR、MCF-7 和白血病 K-562 细胞系表现出更高的抗肿瘤活性，GI50 值均小于 10μg/mL。化合物 11 对 PC-3（GI50=4.31μg/mL）、OVCAR（GI50=8.84μg/mL）和 K-562（GI50=8.80μg/mL）细胞系显示出显著的活性。没食子酰腙（2）在 HepG2/C3A 细胞中具有细胞毒性活性（IC50=153.7μg/mL）。在膜通透性、细胞计数、细胞周期和细胞凋亡测定中，与对照组相比，用 HepG2/C3A 细胞的化合物（2）IC50 确定，观察到膜通透性增加、细胞计数减少、细胞周期改变和早期凋亡。
因此，我们的研究结果首次表明了没食子酰取代化合物的合成、抗增殖活性和细胞毒性。与没食子酰腙（2）相比，没食子酰基取代对抑制癌细胞增殖没有很强的协同作用。化合物 2 在 HepG2/C3A 肝癌细胞中表现出良好的活性。
