Docking experiments suggest that gloriosine has microtubule-targeting properties similar to colchicine

Abstract

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 anLD50 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.

A novel colchicine-myricetin heterozygous molecule: design, synthesis, and effective evaluations on the pathological models of acute lung injury in vitro and in vivo

“…Herb medicine is a great source from which a lot of drugs have been developed. (−)-Colchicine 1) is an iso-quinoline alkaloid isolated from medicinal plants including Colchicum autumnale L. and Gloriosa superba L. ( Misra et al, 2023 ). Originally, colchicine was characterized as a mitotic inhibitor and universally applied in the treatment of cancer.…”