Computational Simulations Highlight the IL2Rα Binding Potential of Polyphenol Stilbenes from Fenugreek.

Widely used in global households, fenugreek is well known for its culinary and medicinal uses. The various reported medicinal properties of fenugreek are by virtue of the different natural phytochemicals present in it. Regarded as a promising target, interleukin 2 receptor subunit alpha (IL2Rα) has been shown to influence immune responses. In the present research, using in silico techniques, we have demonstrated the potential IL2Rα binding properties of three polyphenol stilbenes (desoxyrhaponticin, rhaponticin, rhapontigenin) from fenugreek. As the first step, molecular docking was performed to assess the binding potential of the fenugreek phytochemicals with IL2Rα. All three phytochemicals demonstrated interactions with active site residues. To confirm the reliability of our molecular docking results, 100 ns molecular dynamics simulations studies were undertaken. As discerned by the RMSD and RMSF analyses, IL2Rα in complex with the desoxyrhaponticin, rhaponticin, and rhapontigenin indicated stability. The RMSD analysis of the phytochemicals alone also demonstrated no significant structural changes. Based on the stable molecular interactions and comparatively slightly better MM/PBSA binding free energy, rhaponticin seems promising. Additionally, ADMET analysis performed for the stilbenes indicated that all of them obey the ADMET rules. Our computational study thus supports further in vitro IL2Rα binding studies on these stilbenes, especially rhaponticin.

Design and Synthesis of Anti-Cancer Chimera Molecules Based on Marine Natural Products.

In this paper, the chemical conjugation of marine natural products with other bioactive molecules for developing an advanced anti-cancer agent is described. Structural complexity and the extraordinary biological features of marine natural products have led to tremendous research in isolation, structural elucidation, synthesis, and pharmacological evaluation. In addition, this basic scientific achievement has made it possible to hybridize two or more biologically important skeletons into a single compound. The hybridization strategy has been used to identify further opportunities to overcome certain limitations, such as structural complexity, scarcity problems, poor solubility, severe toxicity, and weak potency of marine natural products for advanced development in drug discovery. Further, well-designed marine chimera molecules can function as a platform for target discovery or degradation. In this review, the design, synthesis, and biological evaluation of recent marine chimera molecules are presented.