Design of Arylsulfonylhydrazones as Potential FabH Inhibitors: Synthesis, Antimicrobial Evaluation and Molecular Docking

2019 ◽  
Vol 15 ◽  
Author(s):  
Thais Batista Fernandes ◽  
Natanael Dante Segretti ◽  
Felipe Rebello Lourenço ◽  
Thalita Marcílio Cândido ◽  
André Rolim Baby ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Molecular Docking ◽  
Antimicrobial Agents ◽  
Acyl Carrier Protein ◽  
Condensation Reaction ◽  
Lung Fibroblast ◽  
Fibroblast Cells ◽  
Human Lung Fibroblast ◽  
Persistent Problem ◽  
E Coli

Background: Antimicrobial resistance is a persistent problem about infections treatment and carries needing for develop new antimicrobial agents. Inhibiting of bacterial β-ketoacyl acyl carrier protein synthase III (FabH), which catalyzes the condensation reaction between a CoA-attached acetyl group and an ACP-attached malonyl group in bacteria is an interesting strategy to find new antibacterial agents. Objective: The aim of this work was to design and synthesize arylsulfonylhydrazones potentially FabH inhibitors and evaluate their antimicrobial activity. Methods: MIC50 of sulfonylhydrazones against E. coli and S. aureus was determined. Antioxidant activity was evaluated by DPPH (1-1’-diphenyl-2-picrylhydrazyl) assay and cytotoxicity against LL24 lung fibroblast cells was verified by MTT method. Principal component analysis (PCA) was performed in order to suggest a structure-activity relationship. Molecular docking allowed to propose sulfonylhydrazones interactions with FabH. Results: The most active compound showed activity against S. aureus and E. coli, with MIC50 = 0.21 and 0.44 µM, respectively. PCA studies correlated better activity to lipophilicity and molecular docking indicated that sulfonylhydrazone moiety is important to hydrogen-bond with FabH while methylcatechol ring performs π-π stacking interaction. The DPPH assay revealed that some sulfonylhydrazones derived from the methylcatechol series had antioxidant activity. None of the evaluated compounds was cytotoxic to human lung fibroblast cells, suggesting that the compounds might be considered safe at the tested concentration. Conclusion: Arylsufonylhydrazones is a promising scaffold to be explored for design of new antimicrobial agents.

Mixed ligand-metal Complexes of 2-(butan-2-ylidene) hydrazinecarbothioamide- Synthesis, Characterization, Computer Aided Drug Character Evaluation and in vitro Biological Activity Assessment

2019 ◽  
Vol 15 ◽  
Author(s):  
Tahmeena Khan ◽  
Rumana Ahmad ◽  
Iqbal Azad ◽  
Saman Raza ◽  
Seema Joshi ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Metal Complexes ◽  
Condensation Reaction ◽  
Dose Range ◽  
Biological Significance ◽  
Mixed Ligand ◽  
Binding Energies ◽  
Mixed Ligand Complexes ◽  
E Coli ◽  
Topo Ii

Background: Mixed ligand-metal complexes are efficient chelating agents because of flexible donor ability. Mixed ligand complexes containing hetero atoms sulphur, nitrogen and oxygen have been probed for their biological significance. Objective: Nine mixed ligand-metal complexes of 2-(butan-2-ylidene) hydrazinecarbothioamide (2-butanone thiosemicarbazone) and pyridine, bipyridine or 2-picoline as co-ligands were synthesized with Cu, Fe and Zn. The complexes were tested against MDA-MB231 (MDA) and A549 cell lines. Antibacterial activity was tested against S. aureus and E. coli. The drug character of the complexes was evaluated on several parameters viz. physicochemical properties, bioactivity scores, toxicity assessment and absorption, distribution, metabolism, excretion and toxicity (ADMET) profile assessment using various automated softwares. Molecular docking of the complexes was also performed with two target proteins. Method and Results: The mixed ligand-metal complexes were synthesized by condensation reaction for 4-5 h. The characterization was done by elemental analysis, 1H-NMR, FT-IR, molar conductance and UV spectroscopies. Molecular docking was performed against ribonucleotide reductase (RR) and topoisomerase II (topo II). [Cu(C5H11N3S)(py)2(CH3COO)2], [Zn(C5H11N3S)(bpy)(SO4)] and [Zn(C5H11N3S)(2-pic)2(SO4)] displayed the lowest binding energies with respect to RR. Against topo II [Cu(C5H11N3S)(py)2(CH3COO)2], [Cu(C5H11N3S)(bpy)(CH3COO)2] and [Zn(C5H11N3S)(2-pic)2(SO4)] had the lowest energies. The druglikness assessment was done using Leadlikeness and Lipinski’s rules. Against topo II [Cu(C5H11N3S)(py)2(CH3COO)2], [Cu(C5H11N3S)(bpy)(CH3COO)2] and [Zn(C5H11N3S)(2-pic)2(SO4)] had the lowest energies. Not more than two violations were obtained in case of each filtering rule showing drug like character of the mixed ligand complexes. Several of the complexes exhibited positive bioactivity scores and almost all the complexes were predicted to be safe with no hazardous effects. All the complexes were predicted to have no mutagenic character as shown by the Ames test [Zn(C5H11N3S)(py)2(SO4)] showed potential activity against MDA. [Co(C5H11N3S(bpy)(Cl)2] was also active against MDA. [Cu(C5H11N3S)(2-pic)2(CH3COO)2] also showed 27.6% cell viability at 100 µM against MDA. Against A549 [Co(C5H11N3S)(py)2(Cl)2], [Cu(C5H11N3S)(py)2(CH3COO)2] and [Co(C5H11N3S(bpy)(Cl)2] were active. [Co(C5H11N3S)(bpy)(Cl)2] and [Cu(C5H11N3S)(2-pic)2(CH3COO)2] were active against S. aureus. [Co(C5H11N3S)(2-pic)2(Cl)2] and [Zn(C5H11N3S)(2-pic)2(SO4)] were active at lower concentrations against S.aureus. Against E. coli, [Zn(C5H11N3S)(2-pic)2(SO4)] showed activity at 18-20mg dose range.

Dynamic protein hydrogels with reversibly tunable stiffness regulate human lung fibroblast spreading reversibly

2019 ◽  
Vol 55 (36) ◽  
pp. 5235-5238 ◽  
Author(s):  
Linglan Fu ◽  
Amanda Haage ◽  
Na Kong ◽  
Guy Tanentzapf ◽  
Hongbin Li
Keyword(s):  
Human Lung ◽  
Lung Fibroblast ◽  
Fibroblast Cells ◽  
Human Lung Fibroblast ◽  
Protein Hydrogels ◽  
Tunable Stiffness

Fibroblast cells change their morphology reversibly in response to changes in protein hydrogel stiffness.

scholarly journals Synthesis, Antimicrobial Activity and Molecular Docking of Novel Thiourea Derivatives Tagged with Thiadiazole, Imidazole and Triazine Moieties as Potential DNA Gyrase and Topoisomerase IV Inhibitors

Molecules ◽  
2020 ◽  
Vol 25 (12) ◽  
pp. 2766 ◽  
Author(s):  
Heba E. Hashem ◽  
Abd El-Galil E. Amr ◽  
Eman S. Nossier ◽  
Elsayed A. Elsayed ◽  
Eman M. Azmy
Keyword(s):  
Antimicrobial Activity ◽  
Molecular Docking ◽  
Antimicrobial Agents ◽  
Biological Activities ◽  
Topoisomerase Iv ◽  
Thiourea Derivatives ◽  
E Coli ◽  
Cytotoxicity Studies ◽  
Ic50 Values

To develop new antimicrobial agents, a series of novel thiourea derivatives incorporated with different moieties 2–13 was designed and synthesized and their biological activities were evaluated. Compounds 7a, 7b and 8 exhibited excellent antimicrobial activity against all Gram-positive and Gram-negative bacteria, and the fungal Aspergillus flavus with minimum inhibitory concentration (MIC) values ranged from 0.95 ± 0.22 to 3.25 ± 1.00 μg/mL. Furthermore, cytotoxicity studies against MCF-7 cells revealed that compounds 7a and 7b were the most potent with IC50 values of 10.17 ± 0.65 and 11.59 ± 0.59 μM, respectively. On the other hand, the tested compounds were less toxic against normal kidney epithelial cell lines (Vero cells). The in vitro enzyme inhibition assay of 8 displayed excellent inhibitory activity against Escherichia coli DNA B gyrase and moderate one against E. coli Topoisomerase IV (IC50 = 0.33 ± 1.25 and 19.72 ± 1.00 µM, respectively) in comparison with novobiocin (IC50 values 0.28 ± 1.45 and 10.65 ± 1.02 µM, respectively). Finally, the molecular docking was done to position compound 8 into the E. coli DNA B and Topoisomerase IV active pockets to explore the probable binding conformation. In summary, compound 8 may serve as a potential dual E. coli DNA B and Topoisomerase IV inhibitor.

scholarly journals Caffeic Acid Protects Hydrogen Peroxide Induced Cell Damage in WI-38 Human Lung Fibroblast Cells

2006 ◽  
Vol 29 (9) ◽  
pp. 1820-1824 ◽  
Author(s):  
Kyoung Ah Kang ◽  
Kyoung Hwa Lee ◽  
Rui Zhang ◽  
Meijing Piao ◽  
Sungwook Chae ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
Caffeic Acid ◽  
Human Lung ◽  
Cell Damage ◽  
Lung Fibroblast ◽  
Fibroblast Cells ◽  
Human Lung Fibroblast

Hormetic effects of noncoplanar PCB exposed to human lung fibroblast cells (HELF) and possible role of oxidative stress

2014 ◽  
Vol 30 (12) ◽  
pp. 1385-1392 ◽  
Author(s):  
Muhammad Zaffar Hashmi ◽  
Kiran Yasmin Khan ◽  
Jinxing Hu ◽  
Naveedullah ◽  
Xiaomei Su ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Human Lung ◽  
Lung Fibroblast ◽  
Fibroblast Cells ◽  
Human Lung Fibroblast

Eosinophil- and Neutrophil-Mediated Injury of Human Lung Fibroblast Cells

1987 ◽  
Vol 83 (4) ◽  
pp. 428-431 ◽  
Author(s):  
R.M. Cook ◽  
R.F. Ashworth ◽  
N.R.J. Musgrove
Keyword(s):  
Human Lung ◽  
Lung Fibroblast ◽  
Fibroblast Cells ◽  
Human Lung Fibroblast

Determination of Chromium in Human Lung Fibroblast Cells Using a Large Bore—Direct Injection High-Efficiency Nebulizer with Inductively Coupled Plasma Mass Spectrometry

2000 ◽  
Vol 54 (5) ◽  
pp. 659-663 ◽  
Author(s):  
John A. McLean ◽  
Billy W. Acon ◽  
Akbar Montaser ◽  
Jatinder Singh ◽  
Daryl E. Pritchard ◽  
...  
Keyword(s):  
Inductively Coupled Plasma ◽  
High Efficiency ◽  
Human Lung ◽  
Direct Injection ◽  
Cell Mass ◽  
Lung Fibroblast ◽  
Fibroblast Cells ◽  
Human Lung Fibroblast ◽  
Inductively Coupled

A novel method for the determination of chromium in suspensions of human lung fibroblast cells is described by using a large bore–direct injection high efficiency nebulizer (LB-DIHEN) with micro-scale flow injection analysis and inductively coupled plasma mass spectrometric detection. Chromium(VI)-treated cells were first counted and then suspended in a phosphate buffer saline solution. With the use of the method of standard additions, the relative concentration of Cr in ∼ 100 HLF cells/peak was determined at m/z = 50. Because the cells tend to clump and can yield inhomogeneities in the total number analyzed, Mg was used as an internal standard to compensate for the total cell mass. The level of Cr in HLF cells grown in a medium of 100 μM Na2CrO4 for two hours is on the order of 180 fg Cr/cell after correction for the number of cells in each injection.

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