title: Synthesis, spectroscopic, dielectric, molecular docking and DFT studies of (3E)-3-(4-methylbenzylidene)-3,4-dihydro-2H-chromen-2-one: an anticancer agent.
abstract: BACKGROUND
  Coumarin (2H-chromen-2-one) and its derivatives have a wide range of biological and pharmaceutical activities. They possess antitumor, anti-HIV, anticoagulant, antimicrobial, antioxidant, and anti-inflammatory activities. Synthesis and isolation of coumarins from different species have attracted the attention of medicinal chemists. Herein, we report the synthesis, molecular structure, dielectric, anticancer activity and docking studies with the potential target protein tankyrase.
  
  
  RESULTS
  Molecular structure of (3E)-3-(4-methylbenzylidene)-3,4-dihydro-2H-chromen-2-one (MBDC) is derived from quantum chemical calculations and compared with the experimental results. Intramolecular interactions, stabilization energies, and charge delocalization are calculated by NBO analysis. NLO property and dielectric quantities have also been determined. It indicates the formation of a hydrogen bonding between -OH group of alcohol and C=O of coumarin. The relaxation time increases with the increase of bond length confirming the degree of cooperation and depends upon the shape and size of the molecules. The molecule under study has shown good anticancer activity against MCF-7 and HT-29 cell lines. Molecular docking studies indicate that the MBDC binds with protein.
  
  
  CONCLUSIONS
  In this study, the compound (3E)-3-(4-methylbenzylidene)-3,4-dihydro-2H-chromen-2-one was synthesized and characterized by spectroscopic studies. The computed and experimental results of NMR study are tabulated. The dielectric relaxation studies show the existence of molecular interactions between MBDC and alcohol. Theoretical results of MBDC molecules provide the way to predict various binding sites through molecular modeling and these results also support that the chromen substitution is more active in the entire molecule. Molecular docking study shows that MBDC binds well in the active site of tankyrase and interact with the amino acid residues. These results are compared with the anti cancer drug molecule warfarin derivative. The results suggest that both molecules have comparable interactions and better docking scores. The results of the antiproliferative activity of MBDC and Warfarin derivative against MCF-7 breast cancer and HT-29 colon cancer cell lines at different concentrations exhibited significant cytotoxicity. The estimated half maximal inhibitory concentration (IC 50) value for MBDC and Warfarin derivative was 15.6 and 31.2 μg/ml, respectively. This enhanced cytotoxicity of MBDC in MCF-7 breast cancer and HT-29 colon cancer cell lines may be due to their efficient targeted binding and eventual uptake by the cells. Hence the compound MBDC may be considered as a drug molecule for cancer.Graphical abstractThe binding mode of the ligand MBDC at active site of protein and the graphical representation of cell inhibition for MCF-7 and HT-29 cell lines.
authors.affiliation: Department of Physics, SRM University, Ramapuram, Chennai, 600089 India.
authors.forename: T
authors.initials: T
authors.lastname: Beena
authors.affiliation: Department of Physics, SRM University, Ramapuram, Chennai, 600089 India.
authors.forename: L
authors.initials: L
authors.lastname: Sudha
authors.affiliation: Department of Physics, SRM University, Ramapuram, Chennai, 600089 India.
authors.forename: A
authors.initials: A
authors.lastname: Nataraj
authors.affiliation: Research Department of Physics, A.A. Government Arts College, Musiri, Tiruchirapalli, 621211 India.
authors.forename: V
authors.initials: V
authors.lastname: Balachandran
authors.affiliation: Department of Organic Chemistry, University of Madras, Guindy Campus, Chennai, 600025 India.
authors.forename: D
authors.initials: D
authors.lastname: Kannan
authors.affiliation: CAS in Crystallography & Biophysics, University of Madras, Guindy Campus, Chennai, 600025 India.
authors.forename: M N
authors.initials: MN
authors.lastname: Ponnuswamy
keywords: Anti-cancer activity; Chromen; DFT; Dielectric studies; Molecular docking