SELECTED NOVEL 5′-AMINO-2′-HYDROXY-1, 3-DIARYL-2-PROPEN-1-ONES ARREST CELL CYCLE OF HCT-116 IN G0/G1 PHASE

A series of 5'-amino-2'-hydroxy-1,3-diaryl-2-propen-1-ones (AC1-AC15) were synthesized by Claisen-Schmidt condensation of 5'-acetamido-2'-hydroxy acetophenone with various substituted aromatic aldehydes. The synthesized compounds were characterized by FTIR, H-1 NMR and mass spectrometry and evaluated for their selective cytotoxicity using MTT assay on two cancer cell lines namely breast cancer cell line (MCF-7), colon cancer cell line (HCT-116) and one normal kidney epithelial cell line (Vero). Among the tested compounds, AC-10 showed maximum cytotoxic effect on MCF-7 cell line with IC50 value 74.7 +/- 3.5 mu M. On HCT-116 cells, AC-13 exhibited maximum cytotoxicity with IC50 value 42.1 +/- 4.0 mu M followed by AC-14 and AC-10 with IC50 values 62 +/- 2.3 mu M and 95.4 +/- 1.7 mu M respectively. All tested compounds were found to be safe on Vero cell line with IC50 value more than 200 mu M. Based on their highest efficacy on HCT-116, AC-10, AC-13 and AC-14 were selected for mechanistic study on this cell line by evaluating changes nucleomorphological characteristics using acridine orange-ethidium bromide (AOEB) dual stain and by analyzing cell cycle with flow cytometry using propidium iodide stain. In AOEB staining, all three tested compounds showed significant (p < 0.05) increase in percentage apoptotic nuclei compared to control cells, with highest increase in apoptotic nuclei by AC-13 treatment (31 %). Flow cytometric studies showed cell cycle arrest by AC-10 and AC-14 treatment in G(0)/G(1) phase and by AC-13 in G(0)/G(1) and G2/M phase. The study reflected the potential of AC-10, AC-13 and AC-14 to be the lead molecules for further optimization.