Semicarbazone derivatives as urease inhibitors: Synthesis, biological evaluation, molecular docking studies and in-silico ADME evaluation

Qazi, Syeda Uroos; Rahman, Shafiq Ur; Awan, Asia Naz; al‐Rashida, Mariya; Alharthy, Rima D.; Asari, Asnuzilawati; Hameed, Abdul; Iqbal, Jamshed

doi:10.1016/j.bioorg.2018.03.029

Cited by 31 publications

(14 citation statements)

References 27 publications

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“…e 1 H NMR and 13 C NMR spectra of the synthesized compounds were recorded in acetone-d 6 and DMSO-d 6 , respectively. In the 1 H NMR spectra of compounds 1-4, the signal of the HC�N proton appeared as a singlet at δ � 8.07-8.23, while the signal of the � N-NH appears as a broad singlet at δ � 9.13-10.04. ese results are similar with the chemical shifts reported for other benzaldehyde and phenoxyphenyl semicarbazone derivatives with the OH, CH 3 , Br, and NO 2 substituents at the phenyl ring [31,35]. e resonance lines of the protons corresponding to the indole ring were observed at δ � 6.83-8.37.…”

Section: Nmr Spectrasupporting

confidence: 87%

“…e NH 2 protons of the thioamide group appeared as a broad singlet in the region δ � 5.98-6.25, in agreement with the chemical shifts found for other semicarbazone derivatives with terminal amine groups [31].…”

Section: Nmr Spectrasupporting

confidence: 84%

“…Synthesis and Characterization. Compounds 1-4 were prepared according to literature [31], as shown in Scheme 1.…”

Section: Resultsmentioning

confidence: 99%

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Indole-3-carbaldehyde Semicarbazone Derivatives: Synthesis, Characterization, and Antibacterial Activities

Carrasco-Solís

Hernández-Gorritti

Chupayo

et al. 2020

Journal of Chemistry

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Four indole-3-carbaldehyde semicarbazone derivatives, 2-((5-bromo-1H-indol-3-yl)methylene)hydrazinecarboxamide (1), 2-((5-chloro-1H-indol-3-yl)methylene)hydrazinecarboxamide (2), 2-((5-methoxy-1H-indol-3-yl)methylene)hydrazinecarboxamide (3), and 2-((4-nitro-1H-indol-3-yl)methylene)hydrazinecarboxamide (4) were synthesized and characterized by ESI-MS and spectroscopic (FT-IR, 1H NMR, and 13C NMR) techniques. The two-dimensional NMR (in acetone-d6) spectral data revealed that the molecules 1 and 2 in solution are in the cisE isomeric form. This evidence is supported by DFT calculations at the B3LYP/6-311++G(d,p) level of theory where it was shown that the corresponding most stable conformers of the synthesized compounds have a cisE geometrical configuration, in both the gas and liquid (acetone and DMSO) phases. The in vitro antibacterial activity of compounds 1–4 was determined against Gram-positive (Staphylococcus aureus and Bacillus subtilis) and Gram-negative (Pseudomonas aeruginosa and Escherichia coli) bacteria. Among all the tested semicarbazones, 1 and 2 exhibited similar inhibitory activities against Staphylococcus aureus (MIC = 100 and 150 μg/mL, respectively) and Bacillus subtilis (MIC = 100 and 150 μg/mL, respectively). On the other hand, 3 and 4 were relatively less active against the tested bacterial strains compared with 1, 2, and tetracycline.

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Section: Nmr Spectrasupporting

confidence: 87%

Section: Nmr Spectrasupporting

confidence: 84%

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Indole-3-carbaldehyde Semicarbazone Derivatives: Synthesis, Characterization, and Antibacterial Activities

Carrasco-Solís

Hernández-Gorritti

Chupayo

et al. 2020

Journal of Chemistry

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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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“…In addition, it is reported that combining steroids (progesterone and testosterone) with semicarbazide or thiosemicarbazide moieties could be a good anticancer drug [38]. Semicarbazones and thiosemicarbazones are a class of Schiff bases that have been gaining considerable attention due to their wide array of pharmacological effects or biological activities [28,29]. In a literature review, we found that semicarbazone based derivatives have shown anticancer, anti-protozoal, antimicrobial, pesticidal activity, etc.…”

Section: Introductionmentioning

confidence: 99%

Novel Steroidal 5α,8α-Endoperoxide Derivatives with Semicarbazone/Thiosemicarbazone Side-chain as Apoptotic Inducers through an Intrinsic Apoptosis Pathway: Design, Synthesis and Biological Studies

Wang

et al. 2020

Molecules

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A series of novel steroidal 5α,8α-endoperoxide derivatives bearing semicarbazone (7a–g) or thiosemicarbazone (7h–k) side chain were designed, synthesized and evaluated for their cytotoxicities in four human cancer cell lines (HepG2, HCT-116, MCF-7, and A549) using the MTT assay in vitro. The results showed that compound 7j exhibited significant cytotoxic activity against HepG2 cells (IC50 = 3.52 μM), being more potent than ergosterol peroxide. Further cellular mechanism studies in HepG2 cells indicated that compound 7j triggered the mitochondrial-mediated apoptosis by decreasing mitochondrial membrane potential (MMP), which was associated with up-regulation of Bax, down-regulation of Bcl-2, activation levels of the caspase cascade, and formation of reactive oxygen species (ROS). The above findings indicated that compound 7j may be used as a promising skeleton for antitumor agents with improved efficacy.

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Semicarbazone derivatives as urease inhibitors: Synthesis, biological evaluation, molecular docking studies and in-silico ADME evaluation

Cited by 31 publications

References 27 publications

Indole-3-carbaldehyde Semicarbazone Derivatives: Synthesis, Characterization, and Antibacterial Activities

Indole-3-carbaldehyde Semicarbazone Derivatives: Synthesis, Characterization, and Antibacterial Activities

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

Novel Steroidal 5α,8α-Endoperoxide Derivatives with Semicarbazone/Thiosemicarbazone Side-chain as Apoptotic Inducers through an Intrinsic Apoptosis Pathway: Design, Synthesis and Biological Studies

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