scholarly journals (Trifluoromethoxy)Phenylboronic Acids: Structures, Properties, and Antibacterial Activity

Molecules ◽  
2021 ◽  
Vol 26 (7) ◽  
pp. 2007
Author(s):  
Agnieszka Adamczyk-Woźniak ◽  
Jan T. Gozdalik ◽  
Ewa Kaczorowska ◽  
Krzysztof Durka ◽  
Dorota Wieczorek ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Spectroscopic Properties ◽  
Docking Studies ◽  
Boronic Acids ◽  
X Ray ◽  
Ortho Isomer ◽  
Intramolecular Hydrogen ◽  
Phenylboronic Acids ◽  
Xrd Method

Three isomers of (trifluoromethoxy)phenylboronic acids were studied in the context of their physicochemical, structural, antimicrobial and spectroscopic properties. They were characterized by 1H, 13C, 11B and 19F NMR spectroscopy. The acidity of all the isomers was evaluated by both spectrophotometric and potentiometric titrations. The introduction of the -OCF3 group influences the acidity, depending, however, on the position of a substituent, with the ortho isomer being the least acidic. Molecular and crystal structures of ortho and para isomers were determined by the single crystal XRD method. Hydrogen bonded dimers are the basic structural motives of the investigated molecules in the solid state. In the case of the ortho isomer, intramolecular hydrogen bond with the -OCF3 group is additionally formed, weaker, however, than that in the analogous -OCH3 derivative, which has been determined by both X-Ray measurements as well as theoretical DFT calculations. Docking studies showed possible interactions of the investigated compounds with LeuRS of Escherichia coli. Finally, the antibacterial potency of studied boronic acids in vitro were evaluated against Escherichia coli and Bacillus cereus.

scholarly journals In silico molecular docking and in vitro antimicrobial efficacy of phytochemicals against multi-drug-resistant enteroaggregative Escherichia coli and non-typhoidal Salmonella spp.

Gut Pathogens ◽  
2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Padikkamannil Abishad ◽  
Pollumahanti Niveditha ◽  
Varsha Unni ◽  
Jess Vergis ◽  
Nitin Vasantrao Kurkure ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Molecular Docking ◽  
In Silico ◽  
Docking Studies ◽  
Antimicrobial Efficacy ◽  
Drug Resistant ◽  
Protein Motifs ◽  
Phytochemical Compounds ◽  
In Silico Molecular Docking

Abstract Background In the wake of emergence of antimicrobial resistance, bioactive phytochemical compounds are proving to be important therapeutic agents. The present study envisaged in silico molecular docking as well as in vitro antimicrobial efficacy screening of identified phytochemical ligands to the dispersin (aap) and outer membrane osmoporin (OmpC) domains of enteroaggregative Escherichia coli (EAEC) and non-typhoidal Salmonella spp. (NTS), respectively. Materials and methods The evaluation of drug-likeness, molecular properties, and bioactivity of the identified phytocompounds (thymol, carvacrol, and cinnamaldehyde) was carried out using Swiss ADME, while Protox-II and StopTox servers were used to identify its toxicity. The in silico molecular docking of the phytochemical ligands with the protein motifs of dispersin (PDB ID: 2jvu) and outer membrane osmoporin (PDB ID: 3uu2) were carried out using AutoDock v.4.20. Further, the antimicrobial efficacy of these compounds against multi-drug resistant EAEC and NTS strains was determined by estimating the minimum inhibitory concentrations and minimum bactericidal concentrations. Subsequently, these phytochemicals were subjected to their safety (sheep and human erythrocytic haemolysis) as well as stability (cationic salts, and pH) assays. Results All the three identified phytochemicals ligands were found to be zero violators of Lipinski’s rule of five and exhibited drug-likeness. The compounds tested were categorized as toxicity class-4 by Protox-II and were found to be non- cardiotoxic by StopTox. The docking studies employing 3D model of dispersin and ompC motifs with the identified phytochemical ligands exhibited good binding affinity. The identified phytochemical compounds were observed to be comparatively stable at different conditions (cationic salts, and pH); however, a concentration-dependent increase in the haemolytic assay was observed against sheep as well as human erythrocytes. Conclusions In silico molecular docking studies provided useful insights to understand the interaction of phytochemical ligands with protein motifs of pathogen and should be used routinely before the wet screening of any phytochemicals for their antibacterial, stability, and safety aspects.

Synthesis, X-ray Diffraction Structures, Spectroscopic Properties, and in vitro Antitumor Activity of Isomeric (1H-1,2,4-Triazole)Ru(III) Complexes

2003 ◽  
Vol 42 (19) ◽  
pp. 6024-6031 ◽  
Author(s):  
Vladimir B. Arion ◽  
Erwin Reisner ◽  
Madeleine Fremuth ◽  
Michael A. Jakupec ◽  
Bernhard K. Keppler ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Spectroscopic Properties ◽  
X Ray Diffraction ◽  
X Ray

scholarly journals The Search for New Antibacterial Agents among 1,2,3-Triazole Functionalized Ciprofloxacin and Norfloxacin Hybrids: Synthesis, Docking Studies, and Biological Activity Evaluation

2021 ◽  
Vol 90 (1) ◽  
pp. 2
Author(s):  
Halyna Hryhoriv ◽  
Illia Mariutsa ◽  
Sergiy M. Kovalenko ◽  
Victoriya Georgiyants ◽  
Lina Perekhoda ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Staphylococcus Aureus ◽  
Biological Activity ◽  
Antibacterial Agents ◽  
Docking Studies ◽  
Synthetic Method ◽  
Bacillus Subtilis Atcc ◽  
Resistant Strains ◽  
Derivatives Of

Among all modern antibiotics, fluoroquinolones are well known for their broad spectrums of activity and efficiency toward microorganisms and viruses. However, antibiotic resistance is still a problem, which has encouraged medicinal chemists to modify the initial structures in order to combat resistant strains. Our current work is aimed at synthesizing novel hybrid derivatives of ciprofloxacin and norfloxacin and applying docking studies and biological activity evaluations in order to find active promising molecules. We succeeded in the development of a synthetic method towards 1,2,3-triazole-substituted ciprofloxacin and norfloxacin derivatives. The structure and purity of the obtained compounds were confirmed by 1H NMR, 13C NMR, 19F NMR, LC/MS, UV-, IR- spectroscopy. Docking studies, together with in vitro research against Staphylococcus aureus ATCC 25923, Escherichia coli ATCC 25922, Bacillus subtilis ATCC 6633, Pseudomonas aeruginosa ATCC 27853, Candida albicans NCTC 885-653 revealed compounds in which activity exceeded the initial molecules.

scholarly journals Synthesis, Molecular Docking and Antimicrobial Activities of 5-(4-substituted-benzyl)-2-(furan/thiophen-2-ylmethylene hydrazono)thiazolidin-4-ones

2021 ◽  
Vol 11 (4) ◽  
pp. 12434-12446
Keyword(s):  
Escherichia Coli ◽  
Molecular Docking ◽  
1H Nmr Spectroscopy ◽  
Antimicrobial Properties ◽  
Antimicrobial Activities ◽  
Docking Studies ◽  
Binding Affinities ◽  
Bacterial Strains ◽  
Effective Synthesis

In our present work, we reported an effective synthesis, molecular docking, and antimicrobial properties of novel 5-(4-substituted-benzyl)-2-(furan/thiophen-2-ylmethylene hydrazono) thiazolidin-4-ones (6a-g) and (7a-i). The structures of the synthesized compounds (6a-g) and (7a-i) were elucidated by 1H-NMR spectroscopy. The molecular docking studies were performed for all the synthesized compounds against GlcN-6P using AutoDock-tools-1.5.6 and recorded the extent of H-bonding and binding affinities. The preselected compounds via molecular docking were further tested for in vitro antimicrobial activity against five bacterial strains (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Staphylococcus aureus) and two fungal strains (Candida albicans and Cryptococcus neoformans). The antimicrobial findings exhibited that the compounds possessed significant antimicrobial potential.

scholarly journals New Application of 1,2,4-Triazole Derivatives as Antitubercular Agents. Structure, In Vitro Screening and Docking Studies

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 6033
Author(s):  
Zbigniew Karczmarzyk ◽  
Marta Swatko-Ossor ◽  
Waldemar Wysocki ◽  
Monika Drozd ◽  
Grazyna Ginalska ◽  
...  
Keyword(s):  
Degrees Of Freedom ◽  
Dipole Moments ◽  
Triazole Ring ◽  
Antimycobacterial Activity ◽  
Docking Studies ◽  
Molecular Structures ◽  
In Vitro Test ◽  
X Ray ◽  
Triazole Derivatives

A series of 1,2,4-triazole derivatives were synthesized and assigned as potential anti-tuberculosis substances. The molecular and crystal structures for the model compounds C1, C12, and C13 were determined using X-ray analysis. The X-ray investigation confirmed the synthesis pathway and the assumed molecular structures for analyzed 1,2,4-triazol-5-thione derivatives. The conformational preferences resulting from rotational degrees of freedom of the 1,2,4-triazole ring substituents were characterized. The lipophilicity (logP) and electronic parameters as the energy of frontier orbitals, dipole moments, NBO net charge distribution on the atoms, and electrostatic potential distribution for all structures were calculated at AM1 and DFT/B3LYP/6-311++G(d,p) level. The in vitro test was done against M. tuberculosis H37Ra, M. phlei, M. smegmatis, and M. timereck. The obtained results clearly confirmed the antituberculosis potential of compound C4, which turned out to be the most active against Mycobacterium H37Ra (MIC = 0.976 μg/mL), Mycobaterium pheli (MIC = 7.81 μg/mL) and Mycobacerium timereck (62.6 μg/mL). Satisfactory results were obtained with compounds C8, C11, C14 versus Myc. H37Ra, Myc. pheli, Myc. timereck (MIC = 31.25−62.5 μg/mL). The molecular docking studies were carried out for all investigated compounds using the Mycobacterium tuberculosis cytochrome P450 CYP121 enzyme as molecular a target connected with antimycobacterial activity.

Synthesis, molecular packing and anti-cholinesterase activity of some new C-2 N-substituted anthranilamide derivatives

2019 ◽  
Vol 234 (9) ◽  
pp. 605-611 ◽  
Author(s):  
Muhammad Sarfraz ◽  
Nargis Sultana ◽  
Muhammad Ilyas Tariq ◽  
Masood Parvez
Keyword(s):  
Hydrogen Bonding ◽  
Cholinesterase Activity ◽  
Intramolecular Hydrogen Bonding ◽  
Pharmacokinetic Profile ◽  
Intermolecular Hydrogen Bonds ◽  
Standard Drug ◽  
X Ray ◽  
Hydrogen Bonding Interactions ◽  
Intramolecular Hydrogen

Abstract Synthesis of C-2 N-substituted anthranilamide derivatives was carried out in a straight forward manner, utilizing 2-aminobenzamide and benzyl chloride as starting materials. Their crystal structures have been established by single crystal X-ray crystallographic method. In the molecules of 2-benzylamino-benzamide (3a), intramolecular hydrogen bonding b/w O atom and proton of –NH and classical intermolecular hydrogen bonding of the type N–H · · · O forming eight membered rings in R42(8) pattern. In both molecules of 2-(dibenzylamino)benzamide (3b), unlike the molecule in 3a, each H atoms is pointed towards N atom causing intramolecular hydrogen bonding interactions, resulting in S(6) motifs. However, it is interesting to note that both molecules in 3b are lying about inversion centres and form dimers in R42(8) motifs; the two dimers are linked via non-classical intermolecular hydrogen bonds C–H · · · O resulting in clusters of four molecules in the structure. In vitro assay results revealed that molecule 3b with IC50 values of 3.8 ± 0.08 μM (AChE) and 17.6 ± 1.10 μM (BChE) possessed better cholinesterase (AChE and BChE) inhibition potential as compared to standard drug galantamine. Preliminary in silico studies showed that more biological active derivatives were also having good pharmacokinetic profile with no AMES toxicity and carcinogenicity.

scholarly journals Synthesis, In Vitro Screening and Docking Studies of New Thiosemicarbazide Derivatives as Antitubercular Agents

Molecules ◽  
2019 ◽  
Vol 24 (2) ◽  
pp. 251 ◽  
Author(s):  
Monika Pitucha ◽  
Zbigniew Karczmarzyk ◽  
Marta Swatko-Ossor ◽  
Waldemar Wysocki ◽  
Maciej Wos ◽  
...  
Keyword(s):  
Spectroscopic Analysis ◽  
Inhibitory Concentration ◽  
Acid Hydrazide ◽  
Docking Studies ◽  
Molecular Structures ◽  
Conformational Preference ◽  
X Ray ◽  
Carboxylic Acid Hydrazide ◽  
Thiosemicarbazide Derivatives

A series of thiosemicarbazide derivatives was designed and synthesized by reaction of carboxylic acid hydrazide with isothiocyanates. The molecular structures of the investigated thiosemicarbazides were confirmed and characterized by spectroscopic analysis. The conformational preference of carbonylthiosemicarbazide chain and intra- and intermolecular interactions in the crystalline state were characterized using X-ray analysis. The antituberculosis activity of the target compounds were tested in vitro against four Mycobacterium strains: M. H37Ra, M. phlei, M. smegmatis, M. timereck. The most active compounds were those with 2-pyridine ring. They exhibited lower minimal inhibitory concentration (MIC) values in the range 7.81–31.25 μg/mL in comparison to the other isomers. Compound 5 had activity against M. smegmatis at a concentration of 7.81 μg/mL whereas compound 2 had activity against all tested strains at a concentration of 15.625 μg/mL. The molecular docking studies were performed for investigated compounds using the Mycobacterium tuberculosis glutamine synthetase MtGS as their molecular target.

Synthesis, crystal structure and docking studies of tetracyclic 10-iodo-1,2-dihydroisoquinolino[2,1-b][1,2,4]benzothiadiazine 12,12-dioxide and its precursors

2020 ◽  
Vol 76 (8) ◽  
pp. 810-820
Author(s):  
Sherif O. Kolade ◽  
Josephat U. Izunobi ◽  
Eric C. Hosten ◽  
Idris A. Olasupo ◽  
Adeniyi S. Ogunlaja ◽  
...  
Keyword(s):  
Deoxyribonucleic Acid ◽  
Docking Studies ◽  
Hydrogen Gas ◽  
Monoclinic Space Group ◽  
Minor Groove Binding ◽  
X Ray Diffraction ◽  
Melting Points ◽  
Groove Binding ◽  
X Ray ◽  
Intramolecular Hydrogen

The title compound, 10-iodo-1,2-dihydroisoquinolino[2,1-b][1,2,4]benzothiadiazine 12,12-dioxide, C15H11IN2O2S (8), was synthesized via the metal-free intramolecular N-iodosuccinimide (NIS)-mediated radical oxidative sp 3-C—H aminative cyclization of 2-(2′-aminobenzenesulfonyl)-1,3,4-trihydroisoquinoline, C15H16N2O2S (7). The amino adduct 7 was prepared via a two-step reaction, starting from the condensation of 2-nitrobenzenesulfonyl chloride (4) with 1,2,3,4-tetrahydroisoquinoline (5), to afford 2-(2′-nitrobenzenesulfonyl)-1,3,4-trihydroisoquinoline, C15H14N2O4S (6), in 82% yield. The catalytic hydrogenation of 6 with hydrogen gas, in the presence of 10% palladium-on-charcoal catalyst, furnished 7. Products 6–8 were characterized by their melting points, IR and NMR (1H and 13C) spectroscopy, and single-crystal X-ray diffraction. The three compounds crystallized in the monoclinic space group, with 7 exhibiting classical intramolecular hydrogen bonds of 2.16 and 2.26 Å. All three crystal structures exhibit centrosymmetric pairs of intermolecular C—H...π(ring) and/or π–π stacking interactions. The docking studies of molecules 6, 7 and 8 with deoxyribonucleic acid (PDB id: 1ZEW) revealed minor-groove binding behaviours without intercalation, with 7 presenting the most favourable global energy of the three molecules. Nonetheless, molecule 8 interacted strongly with the DNA macromolecule, with an attractive van der Waals energy of −15.53 kcal mol−1.

scholarly journals High-Level Production of Porphyrins in Metabolically Engineered Escherichia coli: Systematic Extension of a Pathway Assembled from Overexpressed Genes Involved in Heme Biosynthesis

2003 ◽  
Vol 69 (8) ◽  
pp. 4875-4883 ◽  
Author(s):  
Seok Joon Kwon ◽  
Arjo L. de Boer ◽  
Ralf Petri ◽  
Claudia Schmidt-Dannert
Keyword(s):  
Escherichia Coli ◽  
High Performance ◽  
Protoporphyrin Ix ◽  
Spectroscopic Properties ◽  
Heme Biosynthesis ◽  
Promising Alternative ◽  
High Yields ◽  
High Level

ABSTRACT Due to their spectroscopic properties porphyrins are of special interest for a variety of applications, ranging from drug development or targeting to material sciences and chemical and biological sensors. Since chemical syntheses are limited in terms of regio- and stereoselective functionalization of porphyrins, a biosynthetic approach with tailored enzyme catalysts offers a promising alternative. In this paper, we describe assembly of the entire heme biosynthetic pathway in a three-plasmid system and overexpression of the corresponding genes with Escherichia coli as a host. Without further optimization, this approach yielded remarkable porphyrin production levels, up to 90 μmol/liter, which is close to industrial vitamin B12 production levels. Different combinations of the genes were used to produce all major porphyrins that occur as intermediates in heme biosynthesis. All these porphyrin intermediates were obtained in high yields. The product spectrum was analyzed and quantified by using high-performance liquid chromatography. Intriguingly, although protoporphyrin IX could be produced at high levels, overexpressed Bacillus subtilis ferrochelatase could not convert this substrate appreciably into heme. However, further investigation clearly revealed a high level of expression of the ferrochelatase and a high level of activity in vitro. These results may indicate that heme has a regulatory impact on the iron uptake of E. coli or that the ferrochelatase is inactive in vivo due to an incompatible enzyme interaction.

scholarly journals Cryo soft X-ray tomography to explore Escherichia coli nucleoid remodelling by Hfq master regulator

2021 ◽  
Author(s):  
Antoine Cossa ◽  
Sylvain Trépout ◽  
Frank Wien ◽  
Etienne Le Brun ◽  
Florian Turbant ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Growth Phase ◽  
Noncoding Rna ◽  
Stationary Growth Phase ◽  
Transcriptional Level ◽  
X Ray ◽  
Small Noncoding Rna ◽  
Associated Proteins ◽  
Post Transcriptional Regulation

Bacterial chromosomic DNA is packed within a membrane-less structure, the nucleoid, thanks to proteins called Nucleoid Associated Proteins (NAPs). The NAP composition of the nucleoid varies during the bacterial life cycle and is growth phase-dependent. Among these NAPs, Hfq is one of the most intriguing as it plays both direct and indirect roles on DNA structure. Indeed, Hfq is best known to mediate post-transcriptional regulation by using small noncoding RNA (sRNA). Although Hfq presence in the nucleoid has been demonstrated for years, its precise role is still unclear. Recently, it has been shown in vitro that Hfq belongs to the bridging family of NAPs. Its bridging mechanism relies on the formation of the amyloid-like structure of Hfq C-terminal region. Here, using cryo soft X-ray tomography imaging of native unlabelled cells and using a semi-automatic analysis and segmentation procedure, we show that Hfq significantly remodels the Escherichia coli nucleoid, especially during the stationary growth phase. Hfq influences both nucleoid volume and absorbance. Hfq cumulates direct effects and indirect effects due to sRNA-based regulation of other NAPs. Taken together, our findings reveal a new role for this protein in nucleoid remodelling that may serve in response to stress conditions and in adapting to changing environments. This implies that Hfq regulates nucleoid compaction directly via its interaction with DNA, but also at the post-transcriptional level via its interaction with RNA.

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