title: Selected novel 5'-amino-2'-hydroxy-1, 3-diaryl-2-propen-1-ones arrest cell cycle of HCT-116 in G0/G1 phase.
abstract: 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.
authors.affiliation: Department of Chemistry, Manipal Institute of Technology, Manipal University, Manipal, 576 104, India.
authors.forename: Lalitha
authors.initials: L
authors.lastname: Simon
authors.affiliation: Department of Chemistry, Shri Madhwa Vadiraja Institute of Technology & Management, (affiliated to Visvesvaraya Technological University, Belgaum), Bantakal, Udupi, 574115, India.
authors.forename: K K
authors.initials: KK
authors.lastname: Srinivasan
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, 576 104, India.
authors.forename: Nitesh
authors.initials: N
authors.lastname: Kumar
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, 576 104, India.
authors.forename: Neetinkumar D
authors.initials: ND
authors.lastname: Reddy
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, 576 104, India.
authors.forename: Subhankar
authors.initials: S
authors.lastname: Biswas
authors.affiliation: Department of Pharmacology, Manipal College of Pharmaceutical Sciences, Manipal University, 576 104, India.
authors.forename: C Mallikarjuna
authors.initials: CM
authors.lastname: Rao
authors.affiliation: Department of Pharmaceutical Quality Assurance, Manipal College of Pharmaceutical Sciences, Manipal University, 576 104, India.
authors.forename: Sudheer
authors.initials: S
authors.lastname: Moorkoth
keywords: 5'-amino-2'-hydroxy-1,3-diaryl-2-propen-1-ones; MTT; acridine orange-ethidium bromide nuclear staining; cytotoxicity; flow cytometry