Exploring the anticancer potential of novel chalcone derivatives: Synthesis, characterization, computational analysis, and biological evaluation against breast cancer

Abstract

This study presents a detailed synthesis and in-depth structural analysis of chalcone compounds with putative anticancer activity. The synthesis procedure for (2E)-1-(2,4-dichlorophenyl)-3-(4-methylphenyl) prop‑2-en-1-one (MLDCL), (2E)-1-(4-fluorophenyl)-3-(4-methylphenyl) prop‑2-en-1-one(MLFC) and (2E)-3-(4-methylphenyl)-1-(4-nitrophenyl) prop‑2-en-1-one (MLNC) involves Claisen-Schmidt condensation reaction. Modern analytical methods like FT-IR and H1 NMR spectroscopy were performed for structural characterization and accurate determination of chalcone compounds in the study. Using a UV–Vis-NIR spectrometer, the linear absorption spectra of three crystals were determined. The optical band gap (Eg) value of these chalcones is acquired from the tauc's plot of (αhv)2/3 against (hv). The in silico molecular docking with protein 3EQM provided valuable insights into potential interactions with the created compounds, yielding docking scores ranging from -8.8 to -7.8. Specific amino acid residues, such as ALA438, ALA306, and ILE133, were implicated in these interactions. The top-ranked compound MLNC (TOP1) from docking was further deemed for molecular dynamics studies, MTT assay, apoptosis, and cell cycle studies. The structural dynamics and stability of protein complexes 3EQM-APO, 3EQM-ASD (standard), and 3EQM-TOP1 were assessed over a 300 ns simulation period. Molecular dynamics studies showed that the complex was stable for a complete 300 ns. MTT assay was performed on triple-negative breast cancer cell line MDMAB-231 and normal fibroblast L929 cell line. An apoptosis and cell cycle studies were performed to further confirm the anti-cancer activity of the top-ranked compound MLNC.