Structure and surface analyses of a newly synthesized acyl thiourea derivative along with its <i>in silico</i> and <i>in vitro</i> investigations for RNR, DNA binding, urease inhibition and radical scavenging activities

Khalid, Aqsa; Arshad, Nasima; Channar, Pervaiz Ali; Saeed, Aamer; Mir, Muhammad Ismail; Abbas, Qamar; Ejaz, Syeda Abida; Hökelek, Tuncer; Ejaz, Syeda Abida; Tehzeeb, Arfa

doi:10.1039/d2ra03160d

Cited by 8 publications

(8 citation statements)

References 55 publications

(82 reference statements)

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“…Individual absorption and emission spectra and the cyclic voltammogram of each compound (UP–1-3) were recorded for their optimized concentration (2 × 10 −5 M). Then DNA titrations, upon the compound’s fixed concentration, were carried out in spectrophotometric (UV-visible and fluorescence) and cyclic voltametric (CV) experiments using DNA concentrations ranging from 10 to 70 μM at pH (7.0) and at physiological temperature of 37 °C [ 51 ]. The cells used in these experiments were kept at rest for a few minutes before each run to assure an equilibrium for the compound–DNA complex.…”

Section: Methodsmentioning

confidence: 99%

Investigation of Newly Synthesized Bis-Acyl-Thiourea Derivatives of 4-Nitrobenzene-1,2-Diamine for Their DNA Binding, Urease Inhibition, and Anti-Brain-Tumor Activities

et al. 2023

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Bis-acyl-thiourea derivatives, namely N,N’-(((4-nitro-1,2-phenylene)bis(azanediyl)) bis(carbonothioyl))bis(2,4-dichlorobenzamide) (UP-1), N,N’-(((4-nitro-1,2-phenylene) bis(azanediyl))bis(carbonothioyl))diheptanamide (UP-2), and N,N’-(((4-nitro-1,2-phenylene)bis(azanediyl))bis(carbonothioyl))dibutannamide (UP-3), were synthesized in two steps. The structural characterization of the derivatives was carried out by FTIR, 1H-NMR, and 13C-NMR, and then their DNA binding, anti-urease, and anticancer activities were explored. Both theoretical and experimental results, as obtained by density functional theory, molecular docking, UV-visible spectroscopy, fluorescence (Flu-)spectroscopy, cyclic voltammetry (CV), and viscometry, pointed towards compounds’ interactions with DNA. However, the values of binding constant (Kb), binding site size (n), and negative Gibbs free energy change (ΔG) (as evaluated by docking, UV-vis, Flu-, and CV) indicated that all the derivatives exhibited binding interactions with the DNA in the order UP-3 > UP-2 > UP-1. The experimental findings from spectral and electrochemical analysis complemented each other and supported the theoretical analysis. The lower diffusion coefficient (Do) values, as obtained from CV responses of each compound after DNA addition at various scan rates, further confirmed the formation of a bulky compound–DNA complex that caused slow diffusion. The mixed binding mode of interaction as seen in docking was further verified by changes in DNA viscosity with varying compound concentrations. All compounds showed strong anti-urease activity, whereas UP-1 was found to have comparatively better inhibitory efficiency, with an IC50 value of 1.55 ± 0.0288 µM. The dose-dependent cytotoxicity of the synthesized derivatives against glioblastoma MG-U87 cells (a human brain cancer cell line) followed by HEK-293 cells (a normal human embryonic kidney cell line) indicated that UP-1 and UP-3 have greater cytotoxicity against both cancerous and healthy cell lines at 400 µM. However, dose-dependent responses of UP-2 showed cytotoxicity against cancerous cells, while it showed no cytotoxicity on the healthy cell line at a low concentration range of 40–120 µM.

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Section: Methodsmentioning

confidence: 99%

Investigation of Newly Synthesized Bis-Acyl-Thiourea Derivatives of 4-Nitrobenzene-1,2-Diamine for Their DNA Binding, Urease Inhibition, and Anti-Brain-Tumor Activities

et al. 2023

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“…The crystallographic data of synthesized compound 3 was collected by a diffractometer (Rigaku Oxford Diffraction Xcalibur, Eos, Gemini) equipped with Cu K α radiation ( λ = 1.54184 Å). The same methodology was employed as reported in our previous study ( Khalid et al, 2022 ). The detailed methodology for crystallographic data analysis is given in supplementary data.…”

Section: Methodsmentioning

confidence: 99%

“…We have previously reported the N-((4-acetylphenyl) carbamothioyl)-2,4-dichlorobenzamide derivative ( Figure 1 ) as a possible urease inhibitor based on experimental and computational studies ( Khalid et al, 2022 ). The present work aims to investigate N-((4-acetylphenyl)carbamothioyl) pivalamide 3) as a multi-targeted chemical that might be exploited as a drug-like contender in the future.…”

Section: Introductionmentioning

confidence: 99%

Facile synthesis, crystal structure, biological evaluation, and molecular modeling studies of N-((4-acetyl phenyl) carbamothioyl) pivalamide as the multitarget-directed ligand

et al. 2022

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The crystal structure of N-((4-acetylphenyl)carbamothioyl)pivalamide (3) was synthesized by inert refluxing pivaloyl isothiocyanate (2) and 4-aminoacetophenone in dry acetone. The spectroscopic characterization (1H-NMR, 13CNMR, FT-IR) and single crystal assays determined the structure of synthesized compound (3). Systematic experimental and theoretical studies were conducted to determine the molecular characteristics of the synthesized crystal. The biological examination of (3) was conducted against a variety of enzymes i.e., acetyl cholinesterase (AChE), butyl cholinesterase (BChE), alpha amylase, and urease enzyme were evaluated. The crystal exhibited approximately 85% enzyme inhibition activity against BChE and AChE, but only 73.8 % and 57.9% inhibition activity against urease and alpha amylase was observed respectively. The theoretical calculations were conducted using density functional theory studies (DFTs) with the 6–31G (d, p) basis set and B3LYP functional correlation. The Frontier molecular orbital analysis revealed that the HOMO/LUMO energy gap was smaller, which corresponds to the molecule’s reactivity. In terms of reactivity, the chemical softness value was found to be in good agreement with experimental values. In Crystal structure analysis, the intramolecular N—H•••O hydrogen bond generates a S 6) ring motif and N—H•••O interactions exist in crystal structure between the centroids of neighboring parallel aromatic (C4-C9) rings with a centroid to centroid distance of 3.9766 (7)Å. These intermolecular interactions were useful in structural stabilization. The Hirshfeld surfaces and their related two-dimensional fingerprint plots were used for thorough investigation of intermolecular interactions. According to Hirshfeld surface analysis of the crystal structure the most substantial contributions to the crystal packing are from H ••• O and H ••• N/N ••• H interactions. Molecular docking studies were conducted to evaluate the binding orientation of synthesized crystal with multiple targets. The compound exhibited stronger interactions with AChE and BChE with binding energies of -7.5 and -7.6 kcal/mol, respectively. On the basis of in-vitro and in-silico findings, it is deduced that N-((4-acetylphenyl)carbamothioyl)pivalamide 3) possesses reactive and potent multiple target inhibitory properties.

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“…5). 68 Two novel acyl thiourea N-benzoyl-N 0 -(4-cyanophenyl)thiourea (45) and N-(4-nitrobenzoyl)-N 0 -(4-cyanophenyl)thiourea (46) were synthesized and their structure was determined by single crystal XRD analysis, it was found that the compound (45) crystallized in triclinic crystal system adopting P 1 space group. Crystal packing of the molecules crystal was stabilized by intramolecular C]O/H-N hydrogen bond and intermolecular C]S/H-N and C]S/H-C hydrogen interactions (Fig.…”

Section: Molecular and Crystal Structurementioning

confidence: 99%

“…Baitullina et al synthesized 2,6-dipicolinoylbis(N,N-dialkylthioureas) (174a and 174b) based heterometallic gold metallacages as a platform for the development of nuclear medicine for different (radio)nuclides such as 68 Ga, 177 Lu, and 198 Au. Synthesized metallacages were also screened for their anticancer activity against MCF-7, PC-3, U383 and U343 and it was found that the IC 50 values of metallacages are comparable to auranon.…”

Section: Metallacagesmentioning

confidence: 99%

Exploring the latest trends in chemistry, structure, coordination, and diverse applications of 1-acyl-3-substituted thioureas: a comprehensive review

Ullah,

Saeed,

Azeem

et al. 2024

RSC Adv.

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Structure and surface analyses of a newly synthesized acyl thiourea derivative along with its in silico and in vitro investigations for RNR, DNA binding, urease inhibition and radical scavenging activities

Abstract: A new acyl thiourea derivative was explored for its binding interaction with RNR and DNA and for excellent urease inhibition activity.

Cited by 8 publications

References 55 publications

Investigation of Newly Synthesized Bis-Acyl-Thiourea Derivatives of 4-Nitrobenzene-1,2-Diamine for Their DNA Binding, Urease Inhibition, and Anti-Brain-Tumor Activities

Investigation of Newly Synthesized Bis-Acyl-Thiourea Derivatives of 4-Nitrobenzene-1,2-Diamine for Their DNA Binding, Urease Inhibition, and Anti-Brain-Tumor Activities

Facile synthesis, crystal structure, biological evaluation, and molecular modeling studies of N-((4-acetyl phenyl) carbamothioyl) pivalamide as the multitarget-directed ligand

Exploring the latest trends in chemistry, structure, coordination, and diverse applications of 1-acyl-3-substituted thioureas: a comprehensive review

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