Department of Chemistry, Shahid Beheshti University, General Campus, Tehran, 1983963113, Iran.
Department of Biology, Faculty of Science, University of Guilan, Rasht, Iran.
Daru. 2020 Dec;28(2):591-601. doi: 10.1007/s40199-020-00364-7. Epub 2020 Aug 15.
Cancer as one of the major diseases with high mortality rates threats human life in the world. Subsequently, the design new potent anticancer agents has attracted much attention in the area of synthetic and medicinal chemistry. In this study, new triazol-linked spiroindolinequinazolinone, thiazol-oxindole and oxindole-thiosemicarbazone conjugates were synthesized and evaluated for their in vitro cytotoxic activity toward different cancer lines.
Some new triazol-linked oxindoles and spirooxindoles conjugates were synthesized. The synthesized compounds were tested for their in vitro cytotoxic activity toward cancer lines including A375, PC3, LNCaP, MDA MB231 and normal cells HDF (human dermal fibroblast).
Among all synthesized compounds, the triazol-linked oxindol-thiosemicarbazone conjugate 10b showed the highest cytotoxic activity against different cancer cells. By using quantitative real time PCR (qRT-PCR), it was found that 10b is able to induce apoptosis by alteration of Bax, Bcl2 balance (i.e. by up regulation of Bax and down regulation of Bcl-2 mRNA expression levels). The DAPI staining was used to show the death of cancer cells in the presence of 10b. Interestingly, 10b suppressed the migration of LNCaP cancer cells by up-regulation of epithelial markers (E-cadherin) and down-regulation of mesenchymal markers (vimentin).
Our findings revealed that the compound 10b may be a new potent candidate with multiple biological activities to design therapeutic agents against different cancers. Synthesis and evaluation of in vitro cytotoxic effects of triazol/spiroindolinequinazolinedione, triazol/indolin-3-thiosemicarbazone and triazol/thiazol-indolin-2-one conjugates.
癌症是死亡率较高的主要疾病之一，威胁着全世界人类的生命。因此，设计新型有效的抗癌药物引起了合成和药物化学领域的广泛关注。在这项研究中，我们合成了新的三唑连接的螺吲哚喹唑啉酮、噻唑-氧吲哚和氧吲哚-硫代缩氨基脲化合物，并评估了它们对不同癌细胞系的体外细胞毒性活性。
合成了一些新的三唑连接的氧吲哚和螺氧吲哚化合物。测试了这些合成化合物对 A375、PC3、LNCaP、MDA MB231 和正常细胞 HDF（人真皮成纤维细胞）等癌细胞系的体外细胞毒性活性。
在所合成的化合物中，三唑连接的氧吲哚-硫代缩氨基脲化合物 10b 对不同癌细胞表现出最高的细胞毒性活性。通过定量实时 PCR（qRT-PCR）发现，10b 通过改变 Bax、Bcl2 平衡（即上调 Bax 和下调 Bcl-2 mRNA 表达水平）诱导细胞凋亡。使用 DAPI 染色显示了 10b 存在时癌细胞的死亡。有趣的是，10b 通过上调上皮标志物（E-钙黏蛋白）和下调间充质标志物（波形蛋白）抑制 LNCaP 癌细胞的迁移。
我们的研究结果表明，化合物 10b 可能是一种具有多种生物学活性的新型有效候选物，可用于设计针对不同癌症的治疗药物。三唑/螺吲哚喹唑啉二酮、三唑/吲哚-3-硫代缩氨基脲和三唑/噻唑-吲哚-2-酮化合物的合成和体外细胞毒性效应评价。
