Synthesis, spectroscopic, dielectric, molecular docking and DFT studies of (3E)-3-(4-methylbenzylidene)-3,4-dihydro-2H-chromen-2-one: an anticancer agent

Abstract

BackgroundCoumarin (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.ResultsMolecular 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.ConclusionsIn 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.

Phytochemical profiling, in vitro biological activities, and in silico (molecular docking and absorption, distribution, metabolism, excretion, toxicity) studies of Polygonum cognatum Meissn

“…Thus, coumarin inhibits the growth and proliferation of tumor cells at low concentrations [59,60]. It was reported that some coumarin derivatives have cytotoxic activity and docking studies have revealed that the potential target of coumarin is the tankyrase enzyme [61]. According to the molecular docking results in our study, the binding potential of coumarin to tankyrase shows us that coumarin may act as a potential tankyrase inhibitor.…”

Design, Synthesis and Cytotoxicity of New Coumarin‐1,2,3‐triazole Derivatives: Evaluation of Anticancer Activity and Molecular Docking Studies

“…Furthermore, 4‐hydroxycoumarin was used to reduce the reverse transcriptase activity of ACH‐2‐lymphocyte affected by the HIV [21] and the acylation of hydroxy groups at C‐7&C‐8 positions of 7,8‐dihydroxycoumarin and C‐7 position of the 7‐hydroxycoumarin skeleton were elucidated the changing of G‐protein‐coupled receptor activators into inhibitors [22,23] . Moreover, 3 E ‐3‐(4‐methylbenzylidene)‐3,4‐dihydro‐2H‐chromen‐2‐one and Warfarin derivative were found to an excellent anticancer agent to MCF‐7 and HT‐29 cells with diverse concentrations exhibited considerable cytotoxicity for breast cancer peoples [24] and 7‐(carboxymethoxy)‐4‐methyl coumarin was prescribed to patients who suffered with upper or lower limb i. e., lymphedema disease [25] . Due to heterocyclic conformational discrepancy in the coumarin derivatives of 1,2,3‐Triazole, these compounds project fascinating aspects to have specific binding with tumor cells and to control the growth of cancer cells in mitochondria and human serum albumin [26,28] …”