Synthesis and characterization of new thiosemicarbazones, as potent urease inhibitors: In vitro and in silico studies

Islam, Muhammad; Khan, Ajmal; Shehzad, Muhammad Tariq; Hameed, Abdul; Ahmed, Nadeem; Halim, Sobia Ahsan; Khiat, Mohammed; Anwar, Muhammad U.; Hussain, Javid; Csuk, René; Al‐Harrasi, Ahmed

doi:10.1016/j.bioorg.2019.03.008

Cited by 53 publications

(27 citation statements)

References 30 publications

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“…Further, the experimentally determined values for the O1-C1, O2-C7, O3-C14 and O4-C14 bond lengths were 1.351(18), 1.242(16), 1.212(17) and 1.222 (17) A, respectively, whereas the DFT values of these C-O bond lengths were found to be 1.340, 1.239, 1.215 and 1.212Å, respectively (Table S2 †). The experimentally determined bond angles values for F1-C4-C3, O2-C7-C6, O3-C15-N3, N1-C11-N2, C13-N2-C14 and N3-C15-C10 were 118.2 (13) For 6c, the experimentally determined values for the N1-C11, N1-C12, N2-C15, N2-C16, N3-C12, N3-C16 and N3-C17 bond lengths were 1.332 (19) (18) and 1.470(18)Å, respectively. The DFT values of the above-mentioned bond lengths were found to be 1.333, 1.337, 1.371, 1.380, 1.383, 1.380 and 1.468Å, respectively.…”

Section: Molecular Geometrymentioning

confidence: 90%

“…The structural parameters resulting from DFT calculations were compared with the (Table S1 †). For 6b, the experimentally determined values of the C-N bond lengths for N1-C11, N1-C12, N2-C11, N2-C14 and N3-C15 were 1.336(18), 1.324(19), 1.384(17), 1.367 (19), and 1.378(18)Å, respectively. However, the DFT values of the C-N bond lengths were found to be 1.339, 1.327, 1.386, 1.396 and 1.390Å, respectively (Table S2 †).…”

Section: Molecular Geometrymentioning

confidence: 96%

“…Owing to their biological prominence, substantial effort has been focused towards synthetic strategies for pharmacologically active pyrido [2,3-d] pyrimidines, though there remain many challenges for the synthesis of naturally occurring complex molecules. 2 In continuation of our research work, [16][17][18][19][20] we have synthesized some bioactive nitrogen-and oxygen-containing (hydroxybenzoyl)pyrido [2,3-d] pyrimidine heterocycles. Quantum chemical approaches provided promising insights regarding the chemical and biological systems that oen found good agreement with the experimental results.…”

Section: Introductionmentioning

confidence: 99%

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A facile and concise route to (hydroxybenzoyl)pyrido[2,3-d]pyrimidine heterocycle derivatives: synthesis, and structural, spectral and computational exploration

et al. 2019

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Section: Molecular Geometrymentioning

confidence: 90%

Section: Molecular Geometrymentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

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A facile and concise route to (hydroxybenzoyl)pyrido[2,3-d]pyrimidine heterocycle derivatives: synthesis, and structural, spectral and computational exploration

et al. 2019

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“…During current years, several structural classes of urease inhibitors have been reported including hydroxamic acids, phosphoramidates, urea and thiourea derivatives, oxoindoline and isoindolin‐1‐one derivatives, polyphenols, isoniazids, thiosemicarbazones, benzimidazoles, benzophenone sulfonamides, catechol‐based inhibitors, diflunisal derivatives, aryl urea‐triazole‐based derivatives, 1,3,4‐oxadiazoles, cinnamate‐based phosphonic acids, coumarin‐hybrids, and metal complexes …”

Section: Introductionmentioning

confidence: 99%

Synthesis, Biological Evaluation and Molecular Docking of Deferasirox and Substituted 1,2,4‐Triazole Derivatives as Novel Potent Urease Inhibitors: Proposing Repositioning Candidate

Ashani

Azizian

Alavijeh

et al. 2020

Chemistry & Biodiversity

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A series of new deferasirox derivatives were synthesized through the reaction of monosubstituted hydrazides with 2-(2-hydroxyphenyl)-4H-benzo[e] [1,3]oxazin-4-one. For the first time, deferasirox and some of its derivatives were evaluated for their in vitro inhibitory activity against Jack bean urease. The potencies of the members of this class of compounds are higher than that of acetohydroxamic acid. Two compounds, bearing tetrazole and hydrazine derivatives (bioisoester of carboxylate group), represented the most potent urease inhibitory activity with IC 50 values of 1.268 and 3.254 μM, respectively. In silico docking studies were performed to delineate possible binding modes of the compounds with the enzyme, urease. Docking analysis suggests that the synthesized compounds were anchored well in the catalytic site and extending to the entrance of binding pocket and thus restrict the mobility of the flap by interacting with its crucial amino acid residues, CME592 and His593. The overall results of urease inhibition have shown that these target compounds can be further optimized and developed as a lead skeleton for the discovery of novel urease inhibitors Figure 1. The structure of DFX and its complexation with iron.Scheme 5. The proposed reaction mechanism for the synthesis of DFX and its analogs 7a -7e. two ionic bonds with two Ni 2 + ions. Also, the binding mode of DFX was depicted in Figure 4b, which revealed that like AHA carboxylate group pointed to the bi-nickel ion center. Besides, DFX formed a π -π Figure 2. The location of JBU active site over C-terminal (αβ) 8 TIM barrel domain (a), close-up representation of the active site, the AHA co-crystallized, and the corresponding re-docked form are represented in green and cyan color, respectively (b).Figure 3. Representation of two different docking poses of compounds relative to bi-nickel center over JBU active site: Compounds with 1,2,4-triazole-N 1 -substituted oriented toward the metal center (a), and compounds with 2-hydroxyphenyl pointed one (b). 3,5bis(2-hydroxyphenyl) moiety, related N 1 -substitution and 1,2,4-triazole ring are shown in red, yellow, and navy, respectively.

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“…Thiosemicarbazones (TSCs) are a class of SN donor atom ligands displaying a wide spectrum of biological activities; since they were introduced, they have gained great interest to medicinal chemists . Of those medicinally important TSCs, the tridentate SNN Schiff base ligand pyridine‐2‐carboxaldehyde thiosemicarbazone proved to possess potent anticancer activity .…”

Section: Introductionmentioning

confidence: 99%

Nickel Complexes Bearing SNN and SS Donor Atom Ligands: Synthesis, Structural Characterization and Biological activity

Ibrahim

Farh

Santos

et al. 2019

Applied Organom Chemis

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Based on a tridentate thiosemicarbazone ligand {HL = 4‐(2,4‐dimethylphenyl)‐1‐((pyridin‐2‐yl)methylene)thiosemicarbazide}, the nickel complexes [NiCl(L)] 1, [Ni(L)(diEtdtc)(H2O)] 2 and [Ni(L)(pipdtc)(H2O)] 3 were prepared {NadiEtdtc = sodium diethyldithiocarbamate and Napipdtc = sodium piperidine dithiocarbamate} and their structures were elucidated according to their elemental analyses, solution conductivities, magnetic moments and spectroscopic (IR and electronic) data. X‐ray single crystal studies have confirmed the structure of 1 as a square planar complex in which each nickel atom is linked to three (two nitrogen and one sulfur) atoms from the thiosemicarbazone ligand and a chlorine atom to ensure the complex neutrality. Moreover, the asymmetric unit cell of the complex was found to consist of two independent complex molecules of slightly different conformations (A&B). The complexes, especially the binary one, displayed high bactericidal activities that, in several instances, were comparable to or higher than those of the chloramphenicol standard.

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Synthesis and characterization of new thiosemicarbazones, as potent urease inhibitors: In vitro and in silico studies

Cited by 53 publications

References 30 publications

A facile and concise route to (hydroxybenzoyl)pyrido[2,3-d]pyrimidine heterocycle derivatives: synthesis, and structural, spectral and computational exploration

A facile and concise route to (hydroxybenzoyl)pyrido[2,3-d]pyrimidine heterocycle derivatives: synthesis, and structural, spectral and computational exploration

Synthesis, Biological Evaluation and Molecular Docking of Deferasirox and Substituted 1,2,4‐Triazole Derivatives as Novel Potent Urease Inhibitors: Proposing Repositioning Candidate

Nickel Complexes Bearing SNN and SS Donor Atom Ligands: Synthesis, Structural Characterization and Biological activity

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