Synthesis, <i>In vitro</i> Antiproliferative and Antibacterial Evaluation and Molecular Docking Studies of 6-Chloro-3,4-Dihydro-4-Oxo-2H-Chromen-3-yl Methylene-2-Cyano-3-Phenyl Acryloyl Hydrazide: http://www.doi.org/10.26538/tjnpr/v7i11.39

Mohd Afroz; G. Shiva Kumar

Authors

Mohd Afroz Department of Pharmaceutical Chemistry, GITAM School of Pharmacy, GITAM (Deemed to be University), Sangareddy-502329, India
G. Shiva Kumar Department of Pharmaceutical Chemistry, GITAM School of Pharmacy, GITAM (Deemed to be University), Sangareddy-502329, India

Keywords:

Cancer cell lines, Molecular Docking, Antibacterial, Antiproliferative, Hydrazine derivatives

Abstract

Chromene derivatives containing cyano moiety are heterocyclic compounds with interesting pharmacological activities. The present study aimed to synthesize and determine the pharmacological activity of 6-Chloro-3,4-dihydro-4-oxo-2H-chromen-3-yl methylene-2-cyano-3-phenyl acryloyl hydrazide (3a-o). Compounds 3a – 3o were synthesized following the Knoevenagel condensation and Wolff-Kishner reduction methods. The synthesized compounds were characterized by different spectroscopic techniques including proton and carbon-13 Nuclear Magnetic Resonance (1H- and 13C-NMR) Spectroscopy, Fourier Transform Infrared (FT-IR) Spectroscopy, and Mass Spectrometry (MS). The compounds were screened for their in vitro antiproliferative and antibacterial activities using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) colorimetric assay and agar well diffusion assay, respectively. In silico molecular docking analysis of the compounds were performed against four different proteins; 5C5S, 6XXN, 3K46, and 1MI7 using PyRx0.8 software. Furthermore, their pharmacokinetics (ADMET) properties were predicted using SWISS ADME software. Among the compounds tested, compounds 3b and 3c exhibited the most potent antiproliferative activity against all four cancer cell lines; MCF-7, PC-3, HT-29, SKVO3 with IC50 of 15.28, 13.28, 10.25, and 13.12 μM, respectively for compound 3b, 16.33, 14.16, 12.22, and 14.75 μM, respectively for compound 3c. The standard drug doxorubicin had IC50 of 15.29, 12.26, 9.06, and 13.01 μM, respectively, while 5-Fluorouracil had IC50 of 16.15, 13.73, 10.25, and 14.28 μM, respectively. Most of the compounds showed potent antibacterial activity with their inhibition zone diameter comparable to that of the standard antibiotic ciprofloxacin. Molecular docking analysis gave good binding affinity of the compounds with the target proteins. Physicochemical analysis showed that all the compounds obeyed the Lipinski’s rule of five.

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