title: Synthesis, X-ray crystal structure and anti-tumor activity of calix[n]arene polyhydroxyamine derivatives.
abstract: Calixarene-based compounds are highly effective therapeutic agents against cancer. This study aims to prepare a series of calix [n]arene (n = 4, 6, 8) polyhydroxyamine derivatives (3a-3m) and to study their potential antitumor activities. The single crystal structure of calixs[4]arene derivative 3a was determined through X-ray diffraction. We assessed the ability of the prepared calix [n]arene polyhydroxyamine derivatives to induce cytotoxicity in six cancer cell lines by performing cancer cell growth inhibition assays. Results demonstrated that compounds 3a-3d achieved IC50 values ranging from 1.6 μM to 11.3 μM. Among the different compounds, 3a and 3b exerted the strongest cytotoxic effect in inhibiting the growth of SKOV3 cells. In relation to the underlying mechanisms of cytotoxic effects, cell cycle analysis revealed that the exposure of SKOV3 cells to 3a induced cell cycle arrest in the G0/G1 phase, suggesting a reduction in DNA synthesis. Immunofluorescent staining indicated that the protein expression levels of caspase-3 and p53 in cells significantly increased, whereas that of Bcl-2 was effectively suppressed. Meanwhile, no significant changes in Bax were observed in SKOV3 cells. These results highlight that calixarene 3a can be further studied as a potential anticancer agent.
authors.affiliation: College of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou 225002, PR China; College of Pharmacy, Xuzhou Medical University, Xuzhou 221004, PR China; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: An
authors.affiliation: College of Pharmacy, Xuzhou Medical University, Xuzhou 221004, PR China; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, PR China.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Han
authors.affiliation: College of Pharmacy, Xuzhou Medical University, Xuzhou 221004, PR China; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, PR China.
authors.forename: You-Guang
authors.initials: YG
authors.lastname: Zheng
authors.affiliation: College of Pharmacy, Xuzhou Medical University, Xuzhou 221004, PR China; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, PR China.
authors.forename: Xian-Na
authors.initials: XN
authors.lastname: Peng
authors.affiliation: College of Pharmacy, Xuzhou Medical University, Xuzhou 221004, PR China; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, PR China.
authors.forename: Yun-Sheng
authors.initials: YS
authors.lastname: Xue
authors.affiliation: College of Pharmacy, Xuzhou Medical University, Xuzhou 221004, PR China; Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou 221004, PR China.
authors.forename: Xiao-Ke
authors.initials: XK
authors.lastname: Gu
authors.affiliation: College of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou 225002, PR China.
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.affiliation: College of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou 225002, PR China. Electronic address: cgyan@yzu.edu.cn.
authors.forename: Chao-Guo
authors.initials: CG
authors.lastname: Yan
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D047250:Calixarenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D053148:Caspase 3 / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D054697:Cytostatic Agents / Q000138:chemical synthesis / Q000737:chemistry; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D013329:Structure-Activity Relationship; D016159:Tumor Suppressor Protein p53 / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D054697:Cytostatic Agents; D016159:Tumor Suppressor Protein p53; D047250:Calixarenes; D053148:Caspase 3
keywords: Anti-tumor activity; Calix[n]arene; Polyhydroxyamine derivative