Synthesis, Spectroscopic Characterization, Molecular Docking and in Vitro Cytotoxicity Evaluation Studies on 6-Methoxy-8-Nitroquinoline Hydrogen Sulphate: A Novel Cervical Cancer Drug

The 6-Methoxy-8-nitroquinoline hydrogen sulfate (6M8NQHS) molecule has been studied using density functional theory (DFT) with thorough and accurate vibrational and spectroscopic investigations, as well as experimental validation. FT-IR, FT-Raman, and UV-Vis spectroscopy techniques were used to characterize the synthesized 6M8NQHS sample. The optimized molecular structure and harmonic vibrational frequencies of the molecule were calculated using DFT/B3LYP method with a LANL2DZ basis set using the Gaussian 09 program. The computed and experimental vibrational wavenumbers were assigned. The UV-Vis spectrum absorption spectrum of the molecule was observed in the liquid phase (acetone) and also simulated, which shows the π to π* and n to π* electronic transitions of the molecule. Frontier molecular orbital research reveals the molecule’s molecular reactivity and kinetic stability. The molecule’s reactive site is confirmed by the Mulliken atomic charge distribution and molecular electrostatic potential surface analysis. The bioactivity of the molecule was demonstrated by the natural bond orbital analysis. Molecular docking analysis confirms that the 6M8NQHS molecule inhibits the action of human p38a Mitogen-activated protein kinase 14, which is linked to cervical cancer. In addition, the MTT assay was used to determine the in vitro cytotoxicity of the 6M8NQHS molecule against human cervical cancer cell lines (ME180) and human breast cancer cell lines (MDA MB 231), demonstrating that the title molecule inhibits the cervical cancer cell lines more than breast cancer cell lines. As a result, the current research paves the way for the creation of new drugs to treat cervical cancer.

本研究采用密度泛函理论(Density Functional Theory, DFT)对6-甲氧基-8-硝基喹啉硫酸氢盐(6-Methoxy-8-nitroquinoline hydrogen sulfate, 6M8NQHS)分子开展了系统且精准的振动光谱与谱学研究，并辅以实验验证。研究采用傅里叶变换红外光谱(FT-IR)、傅里叶变换拉曼光谱(FT-Raman)及紫外-可见(UV-Vis)光谱技术对合成的6M8NQHS样品进行了表征。借助Gaussian 09程序，采用DFT/B3LYP方法结合LANL2DZ基组，对该分子的优化分子结构与简谐振动频率进行了计算，并对计算得到的振动波数与实验测得的振动波数完成了归属指认。本研究分别在液相（丙酮溶剂中）观测了该分子的紫外-可见吸收光谱并开展模拟计算，结果显示其存在π→π*与n→π*电子跃迁。前线分子轨道(Frontier Molecular Orbital)研究揭示了该分子的分子反应活性与动力学稳定性；通过马利肯原子电荷分布与分子静电势表面分析，确认了该分子的活性位点。自然键轨道(Natural Bond Orbital)分析验证了该分子的生物活性。分子对接分析证实，6M8NQHS分子可抑制与人宫颈癌相关的人p38α丝裂原活化蛋白激酶14的活性。此外，本研究采用MTT比色法测定了6M8NQHS分子对人宫颈癌细胞系(ME180)及人乳腺癌细胞系(MDA MB 231)的体外细胞毒性，结果表明该标题分子对宫颈癌细胞的抑制效果优于乳腺癌细胞。综上，本研究为开发治疗宫颈癌的新型药物开辟了全新路径。