Pharmacognosy Division, CSIR-National Botanical Research Institute, Rana Pratap Marg, Lucknow, U.P., 226001, India.
Botany Department, North Eastern Hill University, Shillong, 793022, Meghalaya, India.
Sci Rep. 2023 Mar 24;13(1):4854. doi: 10.1038/s41598-023-31187-6.
Gloriosine, the predominant metabolite of Gloriosa superba L., shares chemical properties with colchicine. We analyze the microtubule-binding affinity of gloriosine at the colchicine binding site (CBS) using an in silico-in vivo approach. The In silico docking of gloriosine showed a binding score of (-) 7.5 kcal/Mol towards β-tubulin at CBS and was validated by overlapping the coupling pose of the docked ligand with co-crystallized colchicine. 2D plots (Ligplot +) showed > 85% overlap between gloriosine and colchicine. The ADMET profile of gloriosine was in accordance with Lipinski's rule of five. Gloriosine belongs to class II toxicity with anLD value of 6 mg/kg. In vivo and transmission electron microscopy studies revealed that gloriosine induces abnormalities in cell division such as condensed chromosomes in C-metaphase and enlarged nucleus with increased nuclear material. Gloriosine treated cells exhibited mitotic index of about 14% compared to control of 24% and high anti-proliferative activity i.e. 63.94% cell viability at a low concentration (0.0004 mg/ml). We conclude that gloriosine has a strong affinity for β-tubulin at CBS and thus can be used as a colchicine alternative in cytology and other clinical conditions.
西红花苷,是大鹤望兰中的主要代谢产物,与秋水仙碱具有化学性质相似。我们采用体内外结合的方法分析西红花苷在秋水仙碱结合部位(CBS)与微管的亲和力。西红花苷的分子对接显示,在 CBS 处与β-微管蛋白的结合评分(-)7.5kcal/mol,并通过与共结晶的秋水仙碱偶联构象的重叠进行验证。2D 图谱(Ligplot+)显示,西红花苷与秋水仙碱之间有超过 85%的重叠。西红花苷的 ADMET 特征符合 Lipinski 的五规则。西红花苷属于 II 类毒性,LD 值为 6mg/kg。体内和透射电子显微镜研究表明,西红花苷诱导细胞分裂异常,如 C-中期染色体浓缩和核增大,核物质增加。与对照组的 24%相比,西红花苷处理的细胞有大约 14%的有丝分裂指数,并且在低浓度(0.0004mg/ml)时具有很高的抗增殖活性,即 63.94%的细胞活力。我们得出结论,西红花苷在 CBS 处与β-微管蛋白具有很强的亲和力,因此可以作为细胞学和其他临床情况下秋水仙碱的替代品。