Exploring the complexation by β-cyclodextrin for improving the anticancer potential of leelamine: Experimental and computational approach

초록

Leelamine (LLA) is a natural diterpene alkaloid with promising anticancer activity, particularly against aggressive cancers such as triple-negative breast cancer. However, its therapeutic potential is limited by poor aqueous solubility, instability, and reduced bioavailability, which hinder its clinical translation. Complexation of LLA with beta-Cyclodextrin (BCD) is therefore a necessary strategy to overcome these limitations, enhance its biocompatibility, and potentially augment its anticancer effects. A potentially active water-soluble anti-cancer with biocompatible material from the LLA has been produced in the presence of BCD by the sonication method, and their formation was thoroughly validated using complementary analytical techniques. 1H NMR and ROESY provided direct evidence of complexation, showing that LLA primarily interacts with the outer rim of the BCD cavity rather than achieving complete encapsulation. This observation was further supported by IR, Raman, and NMR analyses, which collectively confirmed the stability of the inclusion complexes (ICs). Surface characterization revealed notable changes in morphology and surface roughness following complex formation. In vitro assays demonstrated that LLA:BCD ICs effectively induced apoptotic cell death in MDA-MB231 triple-negative breast cancer cells, while exhibiting minimal cytotoxicity in normal lung fibroblast cells (MRC-5).

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