In this study, the main aim was synthesis of dimeric compounds, which contain lithocholic acid and a triazole structure to investigate the selective cellular and molecular antiproliferative and proapoptotic potential of these products in healthy embryonic fibroblast (MEF), cervix cancer (HeLa), and breast cancer (MCF-7) cells. Four ester (5a–d) and five dimeric (6a–d, 7) out of nine novel compounds were obtained. First of all, lithocholic acid was converted to methyl lithocholate and then it was reacted with certain alkynoic acids (a–d) to obtain its alkynoate derivatives (5a–d). Finally, these compounds were converted to dimers (6a–d) by using 2,6-bis(azidomethyl)pyridine via the click method. Our result indicate that, treatment with dimeric compounds can selectively decrease the cell viability and proliferation in cervix cancer HeLa and breast cancer MCF-7 cells, except 7 which caused a strong cytotoxicity on healthy MEF cells. According to MTT assay, Nucblue cell stain and Annexin V/Propodium iodide molecular probe staining, 100 µM concentrations of the dimeric compounds was sufficient in inducing death and apoptotic cell ratio in HeLa and MCF-7 breast cancer cells selectively. In brief, the present study indicates that most effective dimeric compounds are 6a and 6b, which have the highest IC₅₀ (345.8–342.6 µM) value on healthy cell and the lowest IC₅₀ value in both cervix (49.2–36.9 µM) and breast (23.0–66.1 µM) cancer cells especially long-term treatment and which triggers apoptosis pathway specifically.

中文翻译：

---

通过点击法合成含有三唑的新型二聚体化合物及其通过线粒体凋亡信号传导的选择性抗增殖和促凋亡潜力

在这项研究中，主要目的是合成包含硫酚酸和三唑结构的二聚体化合物，以研究这些产品在健康胚胎成纤维细胞（MEF），子宫颈癌（HeLa）和乳腺癌（MCF-7）细胞。从九种新化合物中获得了四酯（5a - d）和五聚体（6a - d，7）。首先，将石胆酸转化为石胆酸甲酯，然后将其与某些炔酸（a - d）反应以获得其炔酸衍生物（5a - d）。最后，这些化合物被转化为二聚体（6a – d）通过点击法使用2,6-双（叠氮基甲基）吡啶。我们的结果表明，用二聚体化合物处理可以选择性降低子宫颈癌HeLa和乳腺癌MCF-7细胞的细胞活力和增殖，但7种对健康的MEF细胞具有强烈的细胞毒性。根据MTT分析，Nucblue细胞染色和Annexin V /碘化丙锭分子探针染色，浓度为100 µM的二聚化合物足以选择性地诱导HeLa和MCF-7乳腺癌细胞死亡和凋亡率。简而言之，本研究表明，最有效的二聚化合物是6a和6b，它们具有最高的IC ₅₀健康细胞上的（345.8–342.6 µM）值，子宫颈癌（49.2–36.9 µM）和乳腺癌（23.0–66.1 µM）的IC ₅₀值最低，尤其是长期治疗，并特异性触发细胞凋亡途径。