Design, synthesis and molecular modelling studies of bile acid-curcumin conjugates as potential antiproliferative agents for breast cancer

In this study, novel bile acid–curcumin conjugates (conjugates 3 and 4) were synthesized and structurally characterized using FT-IR, ¹H NMR, and ¹³C NMR spectroscopy. The cytotoxic potential of these conjugates was evaluated against two triple negative breast cancer cell lines (TNBC), 4T1, and MDA-MB-231. Conjugate 3 displayed exceptional cytotoxic activity, with IC₅₀ values of 3.3 ± 0.06 μM for 4 T1 and 0.7 ± 0.01 μM for MDA-MB-231, significantly surpassing the activity of curcumin (IC₅₀ = 29.7 ± 0.9 μM and10.04 μM, respectively). Conjugate 4 also demonstrated enhanced efficacy, with IC₅₀ values of 5.3 ± 0.5 μM (4 T1) and 2.5 ± 0.03 μM (MDA-MB-231). Cell cycle analysis revealed a substantial reduction in the G0/G1 phase population from 89.90 % in untreated cells to 75.10 % for conjugate 3, which induced apoptosis of 37.10 % than curcumin 20.39 % and 75.90 % for conjugate 4, indicating disruption of cell cycle progression and enhanced antiproliferative effects. Both Conjugates 3 and 4 demonstrated excellent biocompatibility, exhibiting no toxicity toward normal macrophages. These findings confirm that bile acid conjugation significantly enhances the antiproliferative potential of curcumin.