Structure-antibacterial Activity Relationship Research Articles

In situ alkali‐free growth of octahedral Ag2O nanoparticles by bacterial cellulose for efficient antibacterial application

AbstractUniform octahedral Ag2O nanoparticles were in situ synthesized within natural bacterial cellulose (BC) films without any inorganic alkali. The morphological transformation of Ag2O from nanoparticles and small nanoplates to an octahedral structure was well controlled by varying the UV exposure time. To reduce and anchor Ag2O nanoparticles, abundant hydroxyl groups on the surface of natural BC fibers ensured an ideal environment for the mild redox reaction between Ag+ and –OH groups. The structural features and structure–activity relationship of Ag2O/BC films were confirmed through TEM, energy dispersive spectroscopy assisted SEM analysis, Fourier transform IR, X‐ray photoelectron spectroscopy, TGA and XRD. The structure–antibacterial activity relationship of the Ag2O/BC films was proved against both Gram‐positive (Staphylococcus aureus) and Gram‐negative (Escherichia coli) bacteria. They also showed excellent performance in the photocatalytic degradation of organic dyes. Ag2O/BC films have potential bactericidal applications in the field of pharmacy, specifically for wound dressing and flexible wearable materials. © 2024 Society of Chemical Industry.

Study on the crystal structure–antibacterial activity relationship of quaternary ammonium Schiff compounds based on difference in their electrostatic potential

Study on the crystal structure–antibacterial activity relationship of quaternary ammonium Schiff compounds based on difference in their electrostatic potential

Design, synthesis, biological evaluation and molecular modeling investigation of new N'-(2-Thiouracil-5-oyl) hydrazone derivatives as potential anti-breast cancer and anti-bacterial agents

A series of novel N’-(2-thiouracil-5-oyl)hydrazones were designed and chemically synthesized using an active substructure combination method. The synthesized compounds were structurally characterized on the basis of elemental (%) analyses, IR, MS, 1H NMR, and 13C NMR spectra. All the prepared compounds were evaluated in vitro against MCF-7 human breast cell line using MTT assay. The anticancer results showed that compounds 3j, 4a, 3c, 3b, and 3h exhibit the most prominent effect against breast cancer cell line with IC50 values of 3.40, 3.50, 3.60, 3.70, and 3.80 µg/ml, respectively using doxorubicin as a control drug. Moreover, molecular docking studies were also performed in order to identify the binding mode mechanism of these compounds with prospective target, thymidylate synthase (PDB:1JU6). On the other hand, the antibacterial activities of all prepared compounds were screened in vitro against three bacterial strains, namely, Escherichia coli, and Pseudomonas aeruginosa as Gram negative bacteria and Staphylococcus aureus as a Gram positive bacterium using agar well diffusion method. The antibacterial activity results revealed that most of the compounds under test were inactive however, among all the tested compounds, only 3g and 4a, in a concentration of 50 µg/ml showed a high antibacterial activity against the three used bacterial strained. It is worthy to note that the potency of 3g against Escherichia coli was comparable to that of the reference drug, while compound 2 exhibited significant activity against Pseudomonas aeruginosa only and compound 3j displayed low activity against Staphylococcus aureus. The structure-antibacterial activity relationship analysis can be modulated by the presence of aromatic or heteroaromatic moiety containing more lipophilic character significantly contributed to antibacterial activity. In addition, the drug-likeness properties have predicted for the target compounds.

Screening and Matching Amphiphilic Cationic Polymers for Efficient Antibiosis.

The amphiphilic cationic polymers that mimic antimicrobial peptides have received increasing attention due to their excellent antibacterial activity. However, the relationship between the structure of cationic polymers and its antibacterial effect remains unclear. In our current work, a series of PEG blocked amphiphilic cationic polymers composed of hydrophobic alkyl-modified and quaternary ammonium salt (QAS) moieties have been prepared. The structure-antibacterial activity relationship of these cationic polymers was investigated against E. coli and S. aureus, including PEGylation, random structure, molecular weights, and the content and lengths of the hydrophobic alkyl side chains. The results indicated that PEGylated random amphiphilic cationic copolymer (mPB35/T57) showed stronger antibacterial activity and better biocompatibility than the random copolymer without PEG (PB33/T56). Furthermore, mPB35/T57 with appropriate mole fraction of alkyl side chains (falkyl = 0.38), degree of polymerization (DP = 92), and four-carbon hydrophobic alkyl moieties was found to have the optimal structure that revealed the best antibacterial activities against both E. coli (MIC = 8 μg/mL, selectivity > 250) and S. aureus (MIC = 4 μg/mL, selectivity > 500). More importantly, mPB35/T57 could effectively eradicate E. coli biofilms by killing the bacteria embedded in the biofilms. Therefore, the structure of mPB35/T57 provided valuable information for improving the antibacterial activity of cationic polymers.

Bioassay-Directed Isolation of Antibacterial Metabolites from an Arthropod-Derived Penicillium chrysogenum.

Bioassay-directed isolation of secondary metabolites from an extract of Penicillium chrysogenum TJ403-CA4 isolated from the medicinally valuable arthropod Cryptotympana atrata afforded five new and 10 known compounds (1-15). All the compounds (except 14) belong to a minor class of highly rigid 6-5-5-5-fused tetracyclic cyclopiane-type diterpenes known to be exclusively produced by members of the Penicillium genus. The structures and absolute configurations of the new compounds (1-5) were elucidated by extensive spectroscopic analyses, including HRESIMS and 1D and 2D NMR, single-crystal X-ray diffraction, and comparison of the experimental electronic circular dichroism data. Compounds 1 and 2 represent the first examples of cyclopianes bearing a C-20 carboxyl group; compound 3 represents the first example of a cyclopiane with a gem-hydroxymethyl group; compound 4 represents the second example of a cyclopiane bearing a hydroxy group at C-7; compound 5 represents the first example of a cyclopiane bearing a hydroxy group at C-8. Compounds 2 and 3 exhibited activity against MRSA, with MIC values of 4.0 and 2.0 μg/mL, respectively. In addition, the structure-antibacterial activity relationship (SAR) of compounds 1-15 is discussed.

Synthesis, antimicrobial activities and computational studies of some oxazolone derivatives

Synthesis of the oxazolone derivatives was achieved by the condensation of aromatic aldehydes with N-acetyl glycine in the presence of acetic anhydride and anhydrous sodium acetate. A total of six oxazolones were synthesized and characterized using 1 H-NMR, 13 C-NMR and FT-IR spectroscopic techniques. The synthesized compounds were screened for their in vitro antibacterial and antifungal activities using streptomycin and ampicillin as control. The result showed that some of the compounds demonstrate good antibacterial activities against specific bacterial strains and moderate activities against other bacterial strains. The compounds did not show any sensitivity against the tested fungal strains. The quantitative structure-antibacterial activity relationship was studied using some quantum chemical parameters with the aid of Spartan 10 (V1.0.1) and XLSTAT (add-in) software. A good correlation was observed between the antibacterial activity of the compounds and the calculated quantum chemical descriptors. Keywords : oxazolones; N-acetyl glycine; antibacterial activity; chemical descriptors.

Effect of Phenolic Compounds on Viability of Wine Spoilage Lactic Acid Bacteria. A Structure-Activity Relationship Study

The effects of wine phenolic compounds (PCs), hydroxybenzoic acids, hydroxycinnamic acids, and a flavanol, on the growth of Lactobacillus hilgardii and Pediococcus pentosaceus, both isolated from Argentine red wine, were assayed in synthetic winelike medium for the first time. The greatest inhibition of L. hilgardii 6F, L. hilgardii X1B, and P. pentosaceus 12p occurred with 400 mg/L of either trans-caffeic or trans-p-coumaric acid and 96 hr of incubation. P. pentosaceus was the most sensitive to PCs. A structure-antibacterial activity relationship study of the PCs revealed that trans-caffeic and trans-p-coumaric acid have similar electron distributions with interatomic distances of 8 A between the catechol hydroxyls and the carboxyl group. These minimum structural requirements (pharmacophore pattern) present in the molecule of the phenolic compounds are necessary to produce antibacterial activity against wine spoilage lactic acid bacteria.

Dibenzo-α-pyrones from the endophytic fungus Alternaria sp. Samif01: isolation, structure elucidation, and their antibacterial and antioxidant activities

The EtOAc extract of the liquid fermentation of Alternaria sp. Samif01, an endophytic fungus obtained from Salvia miltiorrhiza Bunge, showed antibacterial activity against several tested bacterial pathogens. Fractionation of this extract led to the isolation of seven dibenzo-α-pyrones (1–7), including one new compound, 2-acetoxy-2-epi-altenuene (1) and one new natural product, 3-epi-dihydroaltenuene A (2). The structures of the new metabolites were elucidated by comprehensive analysis of the spectroscopic data including (1D, 2D) NMR and HRESIMS, while the absolute configuration of 1 was determined by TDDFT–ECD computation. Altenuisol (5), 4-hydroxyalternariol-9-methyl ether (6), and alternariol (7) showed inhibitory activities against the tested bacteria with minimum inhibitory concentration values in the range of 86.7–364.7 μM. A preliminary structure–antibacterial activity relationship was discussed. In addition, compounds 2, 5 and 6 displayed promising antioxidant effects using DPPH and hydroxyl radical assays. The cytotoxicity of the isolated compounds was evaluated as well.

Structure-Antibacterial Activity Relationships of Imidazolium-Type Ionic Liquid Monomers, Poly(ionic liquids) and Poly(ionic liquid) Membranes: Effect of Alkyl Chain Length and Cations.

The structure-antibacterial activity relationship between the small molecular compounds and polymers are still elusive. Here, imidazolium-type ionic liquid (IL) monomers and their corresponding poly(ionic liquids) (PILs) and poly(ionic liquid) membranes were synthesized. The effect of chemical structure, including carbon chain length of substitution at the N3 position and charge density of cations (mono- or bis-imidazolium) on the antimicrobial activities against both Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) was investigated by determination of minimum inhibitory concentration (MIC). The antibacterial activities of both ILs and PILs were improved with the increase of the alkyl chain length and higher charge density (bis-cations) of imidazolium cations. Moreover, PILs exhibited lower MIC values relative to the IL monomers. However, the antibacterial activities of PIL membranes showed no correlation to those of their analogous small molecule IL monomers and PILs, which increased with the charge density (bis-cations) while decreasing with the increase of alkyl chain length. The results indicated that antibacterial property studies on small molecules and homopolymers may not provide a solid basis for evaluating that in corresponding polymer membranes.

Synthesis and structure–antibacterial activity relationship studies of 4-substituted phenyl-4,5-dihydrobenzo[f][1,4]oxazepin-3(2H)-thiones

The synthesis and characterization of a series of 4-substituted phenyl-4,5-dihydrobenzo[f][1,4]oxazepin-3(2H)-thiones were presented. Preliminary in vitro antimicrobial activity of the compounds was assessed against a panel of microorganisms including S. aureus, E. faecalis, P. aeruginosa, E. coli, and C. albicans. Some of the compounds exhibited significantly in vitro antimicrobial activity. The pMIC values were correlated with physicochemical descriptors: Hammett substituent constants (σ m and σ p ) and the lipophilic constant (π). One statistical significant 2D-QSAR model was obtained with para-substituted compounds. The pMIC values were also correlated with some theoretical descriptors as independent variables and four statistical significant 2D-QSAR models were also obtained with meta-substituted compounds.

Synthesis and structure–antibacterial activity relationship investigation of isomeric 2,3,5-substituted perhydropyrrolo[3,4- d]isoxazole-4,6-diones

The synthesis of 2,3,5-substituted perhydropyrrolo[3,4- d]isoxazole-4,6-diones (44 compounds) has been accomplished by the cycloaddition reaction of N-methyl-C-arylnitrones with N-substituted maleimides. The compounds were screened for their antibacterial activities and most of them exhibited activity against Enterococcus faecalis (ATCC 29212) and Staphylococcus aureus (ATCC 25923). cis - 3a and cis - 3d were found fairly effective against E. faecalis (ATCC 29212) and S. aureus (ATCC 25923) with MIC values of 25 and 50 μg/ml. With the changes of cis isomers of the compounds to trans, their antibacterial activities also changed against the bacteria studied. First, pharmacophoric fragments had been calculated in accordance with the rules of the electronic-topological method (ETM). Next, both active compounds and pharmacophores had been projected to the nodes of Kohonen’s self-organizing maps (SOM) to obtain the weights of pharmacophore fragments as numerical descriptors, that were used after this for the associative neural networks (ASNN) training. A model for the activity prediction was developed as the result of training the ASNNs.

Structure–antibacterial activity relationship of secondary metabolites from Ajuga pseudoiva Rob. leaves

A selection of steroids, glycerides, clerodane diterpenoids, and a β-hydroxy fatty acid methyl ester, all previously isolated from Ajuga pseudoiva leaves, were tested for their antibacterial activity toward three Gram− rods and one Gram+ coccus using the dilution method; MIC values were determined. The results suggested some importance for a free β-hydroxy group in the fatty acid ester and also in the glycerides and clerodane derivatives; the absolute configurations of the latter, notably at C2, had little influence on activity.

Enhanced antitumour activity of 15-residue bovine lactoferricin derivatives containing bulky aromatic amino acids and lipophilic N-terminal modifications.

In a structure-antibacterial activity relationship study of a peptide fragment of bovine lactoferricin consisting of FKCRRWQWRMKKLGA (LFB 17-31), it was revealed that the two Trp residues were important for antibacterial activity. It has further been demonstrated that the size, shape and the aromatic character of the side chains were even more important than the Trp itself. In this study the antitumour effect of a series of LFB 17-31 derivatives are reported, in which the two Trp residues in position 6 and 8 were replaced with the larger non-coded aromatic amino acids Tbt, Tpc, Bip and Dip. The counterproductive Cys in position 3 was also substituted with these larger aromatic residues. In addition, the effect of introducing lipophilic groups of different size and shape in the N-terminal of the LFB 17-31 sequence was addressed. The resulting peptide derivatives were tested for activity against three human tumour cell lines and against normal human umbilical vein endothelial cells and fibroblasts. High antitumour activity by several of the peptides demonstrated that Trp successfully could be substituted by the bulky aromatic residues, and peptides containing the large and rigid Tbt residue in position 6 and/or 8 in LFB 17-31 were the most active candidates. The antitumour effect was even more increased by the Tbt-modified peptides when the three counterproductive amino acids Cys3, Gln7 and Gly14 were replaced by Ala. Enhanced antitumour activity was also obtained by modifying the N-terminal of LFB 17-31 with either long-chained fatty acids or bulky moieties. Thus, our results revealed that the size and shape of the lipophilic groups and their position in the peptide sequence were important for antitumour activity.

Bulky aromatic amino acids increase the antibacterial activity of 15-residue bovine lactoferricin derivatives.

A model peptide, FKCRRWQWRMKKLGA, residues 17-31 of bovine lactoferricin, has been subjected to structure-antibacterial activity relationship studies. The two Trp residues are very important for antibacterial activity, and analogue studies have demonstrated the significance of the size, shape and aromatic character of the side chains. In the current study we have replaced Trp residues in the model peptide with bulky aromatic amino acids to elucidate further the importance of size and shape. The counterproductive Cys residue in position 3 was also replaced by these aromatic amino acids. The largest aromatic amino acids employed resulted in the most active peptides. The peptides containing these hydrophobic residues were generally more active against Staphylococcus aureus than against Escherichia coli, indicating that the bacterial specificity as well as the antibacterial efficiency can be altered by employing large hydrophobic aromatic amino acid residues.

Increased antibacterial activity of 15-residue murine lactoferricin derivatives.

LFM W8 is a synthetic 15-residue lactoferricin derivative (H2N-EKCLRWQWEMRKVGG-COOH), corresponding to residues 16-30 of the mature murine lactoferrin protein except that the asparagine residue in position 8 of the native peptide is replaced with tryptophan. We have previously reported that the two tryptophan residues in positions 6 and 8 are of crucial importance for the antibacterial activity of many lactoferricin derivatives but, despite fulfilling this requirement, LFM W8 is inactive against Escherichia coli and Staphylococcus aureus. In order to solve this puzzle, a quantitative structure-antibacterial activity relationship study of synthetic LFM W8 derivatives was performed by replacing the glutamate residues in positions 1 and 9 with arginine or alanine, and the valine residue in position 13 with tyrosine. The results from the study were analyzed using multivariate data analysis. The derived mathematical model clustered the peptides into distinct groups which reflected their antibacterial activities, pointed out correlations between different structural parameters, highlighted the structural parameters that were important for antibacterial activity, and enabled us to predict the activity of a 15-residue bovine lactoferricin derivative. The results showed that net charge and micelle affinity, as determined from the ratio of alpha-helicity in sodium dodecyl sulfate micelles and in 1,1,1,3,3,3-hexafluoro-2-propanol, were the most important structural parameters affecting antibacterial activity. The most active derivative, LFM R1,9 W8 Y13, displayed a minimal inhibitory concentration of 10 and 12 microM against E. coli and S. aureus, respectively. This represented more than 50-fold and 40-fold increases in antibacterial activity, respectively, compared with LFM W8.

Structure-antibacterial activity relationship of some aromatic acids

Nine aromatic acids were tested for their antibacterial effect against Staphylococcus aureus. 3-phenylpropanoic acid was identified as the most active of the acids chosen for this bioassay. In general a 3,4-methylenedioxy substituent on the phenyl group reduces the activity against Staphylococcus aurens.