Molecular docking, PASS analysis, bioactivity score prediction, synthesis, characterization and biological activity evaluation of a functionalized 2-butanone thiosemicarbazone ligand and its complexes

Abstract

2-Butanone thiosemicarbazone ligand was prepared by condensation reaction between thiosemicarbazide and butanone. The ligand was characterized by H NMR,C NMR, FT-IR, mass spectrometry and UV spectroscopic studies. Docking studies were performed to study inhibitory action against topoisomerase II (Topo II) and ribonucleoside diphosphate reductase (RR) enzymes. Inhibition constants ( ) of the ligand were 437.87 and 327.4 μM for the two enzymes, respectively. The ligand was tested for its potential anticancer activity against two cancer cell lines MDA-MB-231 and A549 using MTT assay and was found to exhibit good activity at higher doses with an IC = 80 μM against human breast cancer cell line MDA-MB-231. On the other hand, no significant activity was obtained against the lung carcinoma cell line A549. Antibacterial activity of the ligand was tested against and using the disc diffusion method. Ligand did not exhibit any significant antibacterial activity. Four complexes of Co(III), Fe(II), Cu(II), and Zn(II) were prepared with the ligand and characterized by various spectroscopic studies. Low molar conductance values were obtained for all complexes displaying non-electrolyte nature except in Co(III) complex. As expected, complexation with metal ions significantly increased the cytotoxicity of the ligand against the tested cell lines viz. IC values of <20 μM for Co, Fe, and Zn complexes and approx. 80 μM against MDA cells versus IC value of <20 μM for Co and Cu complexes and that of 30 and 50 μM for Fe and Zn complexes, respectively, against A549 cells. The Cu complex was found to be active against and with MIC values in the range of 6-10 mg/mL. Other than Cu, only Co complex was found to possess antibacterial activity with MIC values of 5-10 mg/mL when tested against . Bioactivity score and Prediction of Activity Spectra for Substances (PASS) analysis also depicted the drug-like nature of ligand and complexes.

Synthesis, characterization, computational studies and biological activity evaluation of Cu, Fe, Co and Zn complexes with 2-butanone thiosemicarbazone and 1,10-phenanthroline ligands as anticancer and antibacterial agents

“…2-butanone thiosemicarbazone- C 5 H 11 N 3 S . The characterization data of the ligand has already been published in our previous manuscript (Khan et al, 2017[ 22 ]). Colour-Creamish white, Solubility: ethanol, DMSO, DMF Yield 90 %; MW-145; MP (°C) 99.…”

“…The ligand 2-butanone thiosemicarbazone (L 1 ) was prepared using a previously reported procedure with some modifications (Kumar and Kumar; 2013[ 25 ], Khan et al, 2017[ 22 ]). The synthesis of complexes was done in 1:1:1 molar ratio.…”

IN SILICOSCREENING AND MOLECULAR DYNAMIC SIMULATION STUDIES OF POTENTIAL SMALL MOLECULE IMMUNOMODULATORS OF THE KIR2DS2 RECEPTOR

“…Predictably for all the targets except enzyme inhibition, GA20 and GA29 showed greater activity than the standard. Of the three compounds, the standard has the best enzyme inhibition value [34]. Overall, the results show that GA20, GA29 and the standard are good drug candidates (Table 1).…”

The Structure-Based Virtual Screening for Natural Compounds that Bind with the Activating Receptors of Natural Killer Cells

“…Binding ligands could be either agonists or competitive inhibitors. Based on a particular drug target, a compound is considered to be active when it's a bioactivity score is more than 0.0; moderately active when score is between −5.0 and 0.0; and inactive when the score is less than −5.0 [56].…”