Curcumin-Pyrazole Hybrids bearing bis(N-Arylacetamides): Synthesis, Antiproliferative Activity and Cell Cycle Analysis

In present work, a new series of modified curcumin analogs of bis(N-arylacetamides) (6-10) was synthesised in good yields. The synthesised compounds were characterised by spectral data and the curcumin hybrids 6-10 were evaluated in vitro by MTT assay for antiproliferative activity against four different human breast carcinoma cell lines. Compounds 10 and 7 show moderate to better IC50 ± SEM (µM) in the range of 66.52 ± 4.53 to 97.79 ± 3.63 and 71.28 ± 4.30 to 99.18 ± 5.99, respectively against MCF-7, MDA MB-231, MDA MB-436 and MDA MB-453 breast cancerous cell lines. Compounds 10 and 7 have shown a significant inhibition against all the cell lines. Cell cycle analysis of compound 10 in MCF-7 cells revealed a pronounced accumulation of the cell population in the S phase (63.67%), indicating effective S-phase arrest. This suggests that the compound interferes with DNA replication processes. Docking studies with EGFR2 have shown higher glide scores, -5.857 and -5.448 kcal/mol, respectively, for compounds 10 and 7. The results indicate that the curcumin-pyrazole bis(N-arylacetamide) hybrid adducts as a promising lead to develop as antiproliferative agents.