Coordination compounds of pyrazolone‐based ligand: Design, characterization, biological evaluation, antitumor efficiency, and DNA binding evaluation supported by in silico studies

Abstract

Cu (II), Ni (II), Mn (II), and Cr (III) chelates of the organic ligand named 3-(furan-2-yl)-5-oxo-N,1-diphenyl-4,5-dihydro-1H-pyrazole-4-carbothioamide ligand (abbreviated as H 2 L) have been obtained. Successful structure elucidation of the ligand and its chelates has been managed by applying alternative spectral and analytical techniques including elemental analysis, inductively coupled plasma (ICP), NMR, mass, and FTIR spectra in addition to molar conductance and TGA technique which all joint confirmed the formation of the metal complexes in the molar ratio 1:2 (M:L) for Cu (II) and Mn (II) chelates, while 1:1 for the rest of complexes. The applied techniques also confirmed the metal complexes to be formulated as [Cu (HL) where HL is the organic ligand. UV-Vis spectra and μ eff values of the metal chelates assured the geometry around the metal ion center to be octahedral for both Cu (II), Mn (II), and Cr (III) complexes. For the Ni (II) complex, tetrahedral arrangement has been concluded. The in vitro antimicrobial efficacy applied on several microorganisms and the antioxidant activity showed biological activities in relation to employed standard reported compounds with enhanced activity of the Cr (III) complex compared with the other tested compounds. The antitumor activity was examined upon four carcinoma cell lines that are HePG-2 MCF-7, HCT-116, and HeP-2 demonstrated that the Cr (III) complex to has the highest activity against the four tested carcinoma cell lines relative to the other tested compounds. The binding mode of the ligand and its complexes with SS-DNA have been examined applying UV-Vis spectral titration and viscosity measurements, assuring groove binding interactions, which were supported theoretically through the docking studies.

Design, spectral, thermal decomposition, antimicrobial, docking simulation and DNA binding tendency of sulfisoxazole azo dye derivative and its metal chelates with Mn2+, Fe3+, Co2+, Ni2+, Cu2+, Zn2+ and Cd2+

“…If the mode of binding of the DNA with the target molecule is intercalation, groove or electrostatic interaction, the observed spectral behaviour is hypochromism ‘intercalation is usually associated with a red‐shift’, whereas hyperchromism occurs when there is structural damage to the double helix of DNA. [ 28 ]…”

“…Confirmation of the nonexistence of protein in the structure of DNA was utilized spectroscopically, by determination of the ratio of absorbance at λ equal to 260 and 280 nm (A 260 /A 280 ) that has been calculated to be between 1.8 and 1.9. [ 28 ] The tools that have been used for investigating the DNA binding manners of the interested compounds are absorption spectroscopy and viscosity measurements. Details of the methodology of both tests are presented in Section S3.…”

“…If the mode of binding of the DNA with the target molecule is intercalation, groove or electrostatic interaction, the observed spectral behaviour is hypochromism 'intercalation is usually associated with a red-shift', whereas hyperchromism occurs when there is structural damage to the double helix of DNA. [28] Experiments of the absorption titration are performed using a concentration of the compounds under study of 50 μM, which is kept constant during the experiment, whereas the SS-DNA concentration is altered using concentrations in the range 5-45 μM at room temperature. SS-DNA absorbance is annulled through addition of equivalent concentration of SS-DNA to both test and reference solutions.…”

In Vitro Antimicrobial Evaluation, Single-Point Resistance Study, and Radiosterilization of Novel Pyrazole Incorporating Thiazol-4-one/Thiophene Derivatives as Dual DNA Gyrase and DHFR Inhibitors against MDR Pathogens

“…First, the docking process was performed using Molecular Operating Environmental (MOE) 10.2008. − The most active pyrazole-thiazolinone derivatives 4a , 5a , 10 , and 13 , and pyrazole-thiophene derivative 7b were built using Chembiodraw 2014 and exported to MOE. The protein structures of DNA gyrase (PDB: 2XCT) and DHFR (PDB: 1DLS) were obtained from the protein data bank ().…”

A new exploration toward adamantane derivatives as potential anti‐MDR agents: Design, synthesis, antimicrobial, and radiosterilization activity as potential topoisomerase IV and DNA gyrase inhibitors

“…Molecular docking studies for the most active adamantane derivatives and positive control (CIP and NV) were evaluated inside the active site of DNA gyrase (PDB: 4URO) and topoisomerase IV (PDB: 4EMV) using Molecular operating Environmental (MOE; Rizk et al, 2021). First, the structure of the synthesized adamantane and positive controls were built using chembiodraw 2014 and then exported to MOE, where the hydrogen bond was added, and the structure exposed to energy was minimized using MMFF94x forcefield as described previously (Ezzat et al, 2022; Ibrahim et al, 2022; Khattab et al, 2022). The active site of DNA gyrase (PDB: 4URO) was generated according to the previously reported method (Alotaibi & Amer, 2020; Fayed et al, 2022), where the trigonal matcher placement method was used to generate the optimized 3D structure of ligand inside the active site of pocket.…”