分析化学2026，Vol.54Issue(8)：1365-1377,中插12-中插23,25.DOI:10.19756/j.issn.0253-3820.251255
基于DNA相互作用的17-芳香席夫碱取代的孕甾衍生物合成及抗肿瘤活性
Synthesis and Antitumor Activity of 17-Aromatic Schiff Base-Substituted Pregnan Derivatives Based on DNA Interactions
摘要
Abstract
The investigation of steroid-DNA interaction is very important for designing an improved therapeutic agent.In this work,five novel 17-aromatic schiff base-substituted pregnan derivatives(1-5)were synthesized,and the antiproliferative activity in vitro and interaction with calf thymus DNA(ct-DNA)were studied.The 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide(MTT)assay showed that compounds 1 and 2 had better antitumor activity than other compounds against some carcinoma cell lines,and exhibited less cytotoxicity on normal human cells.In particular,the IC50 values of compounds 1 and 2 were(4.72±0.09)and(1.17±0.01)μmol/L against human ovarian carcinoma(SKOV3)cell line.Furthermore,fluorescence spectroscopy experimental results showed that compounds 1 and 2 bound to DNA preferentially through hydrophobic and π-π stacking interactions with binding constant(Kb)of 9.10×104 L/mol and 1.06×105 L/mol,respectively,indicating the higher binding affinity of compound 2 towards DNA.The ethidium bromide(EB)and Hoechst 33258 competitive binding experiments showed that intercalation should be the major binding mode of compounds 1 and 2 with DNA.The binding mode was further supported by circular dichroism spectrum analysis,viscosity measurements and molecular docking.The results of this work provided references for design and development of steroid antitumor drugs.关键词
孕烯醇酮/席夫碱/小牛胸腺DNA/插入作用/抗肿瘤活性Key words
Pregnenolone/Schiff base/Calf thymus DNA/Intercalation/Antitumor activity引用本文复制引用
甘春芳,钟智薇,赵杰,文舒婷,黄采佳,展军颜..基于DNA相互作用的17-芳香席夫碱取代的孕甾衍生物合成及抗肿瘤活性[J].分析化学,2026,54(8):1365-1377,中插12-中插23,25.基金项目
广西自然科学基金项目(Nos.2023GXNSFAA026399,2023GXNSFDA026063)、国家自然科学基金项目(No.22467017)和2025年大学生创新训练计划资助项目资助. Supported by the Guangxi Natural Science Foundation(Nos.2023GXNSFAA026399,2023GXNSFDA026063),the National Natural Science Foundation of China(No.22467017)and the College Students' Innovation Training Program in 2025. （Nos.2023GXNSFAA026399,2023GXNSFDA026063）
