羽扇豆甙（PLM）是一种植物衍生物，在人类中被广泛应用于治疗多种疾病，具有抗癌、抗炎、抗氧化和抗菌等多种疗效。虽然已对该植物化学物质的细胞毒性和基因毒性进行了研究，但仍需要进一步的认识。由于DNA是多种药物的重要靶标，因此选取DNA来研究其与PLM对细胞系统的影响。紫外-可见光谱学表明PLM与ctDNA结合，染料置换实验进一步证实了PLM-ctDNA复合物的形成。圆二色谱光谱的无明显变化表明PLM不影响ctDNA的结构组成，因此结合可能是外围结合而非穿插结合。此外，相对粘度和复合物形成后熔融温度的微小变化支持了这一发现，并进一步确认了PLM的沟槽结合。分子对接分析和模拟研究也表明PLM为DNA的小沟槽结合剂，并提供了PLM-DNA复合物的相互作用动力学细节。对接和100 ns模拟后显示出负 Gibbs 自由能变化 (∆G = -6.6 kcal mol-1)，以及稳定复合物的形成。稳定动力学的PLM-DNA复合物还得到了RMSD、RMSF、SASA、Rg和相互作用能量剖面等不同参数的支持。本研究揭示了PLM的细胞毒性和基因毒性机制，对于挖掘其在包括癌症在内的多种疾病治疗中的潜力，具有重要意义。版权所有 © 2023 年 Rahaman, Anjum, Kumari, Shafie, Alee, Badr, Khan, Ashour, Hazazi, Arif和Zeng。

Plumbagin (PLM), a plant derivative, is well known for a wide range of therapeutic effects in humans including anti-cancer, anti-inflammatory, anti-oxidant, and anti-microbial. Cytotoxic and genotoxic potential of this phytochemical has been studied which demands further insight. DNA being a major target for several drugs was taken to study against PLM to understand its effects on the cellular system. UV-Vis spectroscopy has indicated the binding of PLM to ctDNA and dye displacement assays have confirmed the formation of PLM-ctDNA complex. The insignificant changes in circular dichroism spectra suggested that PLM is not affecting the structural makeup of the ctDNA, hence the binding could be peripheral and not intercalating. Further, the relative viscosity and minimal change in melting temperature upon the complex formation supported this finding and confirmed the groove binding of PLM. Molecular docking analysis and simulation studies also show PLM as a minor groove binder to DNA and provide details on the interaction dynamics of PLM-DNA complex. Docking followed by a 100 ns simulation reveals the negative Gibbs free energy change (∆G = -6.6 kcal mol-1), and the formation of a stable complex. The PLM- DNA complex with stable dynamics was further supported by different parameters including RMSD, RMSF, SASA, Rg, and the energy profile of interaction. This study provides an insight into the cytotoxic and genotoxic mechanism of PLM which can be a crucial step forward to exploit its therapeutic potential against several diseases including cancer.Copyright © 2023 Rahaman, Anjum, Kumari, Shafie, Alee, Badr, Khan, Ashour, Hazazi, Arif and Zeng.