Synthesis of <i>S</i>-2-phenylchromane Derivatives and Evaluation of the Antiproliferative Properties as Apoptosis Inducers in Cancer Cell Lines

Author(s):

Yunfeng Zhang, Jiale Ma, Yujie Pei, Zeyuan Xie, Dong-Jun Fu* and Jun Li*   Pages 1848 - 1859 ( 12 )

Abstract:

<p>Background: Cancer remains one of the major health issues globally, where chemotherapy forms the main treatment mode for different types of cancers. Due to cancer cell ability to develop resistance, decreased clinical effectiveness of anticancer drugs can occur. Therefore, the need to synthesize novel antitumor drugs remains important. <p> Objective: The aim of our work consisted of synthesizing S-2-phenylchromane derivatives containing the tertiary amide or 1,2,3-triazole fragments with promising anticancer activity. <p> Methods: A series of S-2-phenylchromane derivatives were synthesized and evaluated for cytotoxic activity against three selected cancer cell lines (HGC-27 human gastric carcinoma cell line, Huh-7 epithelial-like tumorigenic cells, and A549 adenocarcinomic human alveolar basal epithelial cells) using the 3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide (MTT) assay. Hoechst staining was used to detect the effects of S-2-phenylchromane derivatives on apoptosis. The apoptosis percentages were detected by annexin V-fluoresceine isothiocyanate/propidium iodide (Annexin V-FITC/PI) double staining assay with flow cytometry. Expression levels of apoptosis-related proteins were detected by western blot. <p> Results: Cell line A549, consisting of adenocarcinomic human alveolar basal epithelial cells, displayed the highest sensitivity to the S-2-phenylchromane derivatives. Among these compounds, E2 showed the most potent antiproliferative activity against A549 cells with an IC₅₀ value of 5.60 μM. Hoechst staining and flow cytometry analysis revealed apoptosis in A549 cells by compound E2. In addition, activation of the expression levels of caspase-3, caspase-7, and their substrate poly (ADP-ribose) polymerase (PARP) by E2 was detected by western blot. <p> Conclusion: In summary, results point towards compound E2, an S-2-phenylchromane derivative, as a potential lead molecule in anticancer agents for human adenocarcinomic alveolar basal cells based on the induction of apoptosis.

Keywords:

S-2-phenylchromane, tertiary amide, triazole, anticancer agents, A549 adenocarcinomic human alveolar basal cells, compound E2, apoptosis.

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