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2016 ; 15
(ä): 21-32
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Selected novel 5 -amino-2 -hydroxy-1, 3-diaryl-2-propen-1-ones arrest cell cycle
of HCT-116 in G0/G1 phase
#MMPMID27152112
Simon L
; Srinivasan KK
; Kumar N
; Reddy ND
; Biswas S
; Rao CM
; Moorkoth S
EXCLI J
2016[]; 15
(ä): 21-32
PMID27152112
show ga
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, (1)H 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 µM. On HCT-116 cells, AC-13 exhibited maximum cytotoxicity with IC50 value
42.1 ± 4.0 µM followed by AC-14 and AC-10 with IC50 values 62 ± 2.3 µM and 95.4 ±
1.7 µM respectively. All tested compounds were found to be safe on Vero cell line
with IC50 value more than 200 µM. 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 G0/G1 phase and by AC-13 in G0/G1 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.