Synthesis,Biological Evaluation and 2D-QSAR Study of Halophenyl Bis-Hydrazones as Antimicrobial and Antitubercular Agents

In continuation of our endeavor towards the development of potent and effective antimicrobial agents, three series of halophenyl bis-hydrazones (14a–n, 16a–d, 17a and 17b) were synthesized and evaluated for their potential antibacterial, antifungal and antimycobacterial activities. These efforts led to the identification of five molecules 14c, 14g, 16b, 17a and 17b (MIC range from 0.12 to 7.81 μg/mL) with broad antimicrobial activity against Mycobacterium tuberculosis; Aspergillus fumigates; Gram positive bacteria, Staphylococcus aureus, Streptococcus pneumonia, and Bacillis subtilis; and Gram negative bacteria, Salmonella typhimurium, Klebsiella pneumonia, and Escherichia coli. Three of the most active compounds, 16b, 17a and 17b, were also devoid of apparent cytotoxicity to lung cancer cell line A549. Amphotericin B and ciprofloxacin were used as references for antifungal and antibacterial screening, while isoniazid and pyrazinamide were used as references for antimycobacterial activity. Furthermore, three Quantitative Structure Activity Relationship (QSAR) models were built to explore the structural requirements controlling the different activities of the prepared bis-hydrazones.     

Evaluation of Antibacterial Activity of Nanostructured Copolymers of Poly (Naphthylamine)

The present preliminary investigation highlights for the first time the antibacterial activity of copolymers of nanostructured poly (naphthylamine) (PNA) with aniline (PNA-co-PANI) and o-toluidine (PNA-co-POT) against E. coli and S. aureus. The antibacterial effect of these nanosized polymers was found to be much higher than that reported for pristine polyaniline. The chemical structure and morphology of the copolymers was found to play a significant role in deciding the antimicrobial efficiency of the copolymers. A proposed mechanism of antimicrobial effect has also been suggested. Our results indicate that the antimicrobial effects of the copolymers could be useful ingredients for biomaterials used in the development of food packaging and medical devices.     

Synthesis and antimicrobial activity of Schiff base of chitosan and acylated chitosan

Chitosan, a biocompatible, biodegradable, nontoxic polymer, is prepared from chitin, which is the second most naturally occurring biopolymer after cellulose. Schiff base of chitosan, sorbyl chitosan, and p‐aminobenzoyl chitosan were synthesized working under high‐intensity ultrasound and their antimicrobial properties were analyzed against Escherichia coli, Staphylococcus aureus, and Aspergillus niger. The structures of the derivatives were characterized by FTIR spectroscopy and elemental analysis. The results of antimicrobial activities indicated that the antimicrobial activities of the derivatives increased with increasing the concentration. The antibacterial activity of schiff base of chitosan against E. coli was stronger, while acylated chitosan had better inhiting effect on S. aureus than others. It was also found that the antifungal activities of the derivatives were stronger than that of chitosan, and schiff base of chitosan was obviously superior to acylated chitosan. © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2012     

New 14-Membered Cyclopeptide Alkaloids from Zizyphus oxyphylla Edgew

Two new 14-membered cyclopeptide alkaloids, Oxyphylline B (4) and Oxyphylline C (5), along with three known 13-membered cyclopeptide alkaloids, were isolated from stem and roots of Zizyphus oxyphylla Edgew. The compounds were tested for antibacterial activity. Oxyphylline B (4) showed comparatively better antibacterial activities against Escherichia coli (MIC, 5 μg/mL) than other compounds. This compound also exhibited weak antimicrobial activities against Staphylococcus aureus (MIC, 25 μg/mL), Pseudomonas aeruginosa (MIC, 50 μg/mL) and Salmonella typhi (MIC, 50 μg/mL).     

Adhesive Antimicrobial Peptides Containing 3,4-Dihydroxy-L-Phenylalanine Residues for Direct One-Step Surface Coating

Bacterial colonization and transmission via surfaces increase the risk of infection. In this study, we design and employ novel adhesive antimicrobial peptides to prevent bacterial contamination of surfaces. Repeats of 3,4-dihydroxy-L-phenylalanine (DOPA) were added to the C-terminus of NKC, a potent synthetic antimicrobial peptide, and the adhesiveness and antibacterial properties of the resulting peptides are evaluated. The peptide is successfully immobilized on polystyrene, titanium, and polydimethylsiloxane surfaces within 10 min in a one-step coating process with no prior surface functionalization. The antibacterial effectiveness of the NKC-DOPA₅-coated polystyrene, titanium, and polydimethylsiloxane surfaces is confirmed by complete inhibition of the growth of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus within 2 h. The stability of the peptide coated on the substrate surface is maintained for 84 days, as confirmed by its bactericidal activity. Additionally, the NKC-DOPA₅-coated polystyrene, titanium, and polydimethylsiloxane surfaces show no cytotoxicity toward the human keratinocyte cell line HaCaT. The antimicrobial properties of the peptide-coated surfaces are confirmed in a subcutaneous implantation animal model. The adhesive antimicrobial peptide developed in this study exhibits potential as an antimicrobial surface-coating agent for efficiently killing a broad spectrum of bacteria on contact.     

Quasi-Diamond Platelet-Shaped Zinc Oxide Nanostructures Display Enhanced Antibacterial Activity

The current study compares the antibacterial activity of zinc oxide nanostructures (neZnO). For this purpose, two bacterial strains, Escherichia coli (ATCC 4157) and Staphylococcus aureus (ATCC 29213) were challenged in room light conditions with the aforementioned materials. Colloidal and hydrothermal methods were used to obtain the quasi-round and quasi-diamond platelet-shape nanostructures. Thus, the oxygen vacancy (V_O) effects on the surface of neZnO are also considered to assess its effects on antibacterial activity. The neZnO characterization was achieved by X-ray diffraction (XRD), a selected area electron diffraction (SAED) and Raman spectroscopy. The microstructural effects were monitored by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Furthermore, optical absorption ultraviolet visible spectrophotometry (UV-Vis) and X-ray photoelectron spectroscopy (XPS) analyses complement the physical characterization of these nanostructures; neZnO caused 50 % inhibition (IC₅₀) at concentrations from 0.064 to 0.072 mg/mL for S. aureus and from 0.083 to 0.104 mg/mL for E. coli, indicating an increase in activity against S. aureus compared to E. coli. Consequently, quasi-diamond platelet-shaped nanostructures (average particle size of 377.6±10 nm) showed enhanced antibacterial activity compared to quasi-round agglomerated particles (average size of 442.8±12 nm), regardless of Vo presence or absence.     

Prenylated Flavonoids with Potential Antimicrobial Activity: Synthesis,Biological Activity,and In Silico Study

Prenylated flavonoids are an important class of naturally occurring flavonoids with important biological activity, but their low abundance in nature limits their application in medicines. Here, we showed the hemisynthesis and the determination of various biological activities of seven prenylated flavonoids, named 7–13, with an emphasis on antimicrobial ones. Compounds 9, 11, and 12 showed inhibitory activity against human pathogenic fungi. Compounds 11, 12 (flavanones) and 13 (isoflavone) were the most active against clinical isolated Staphylococcus aureus MRSA, showing that structural requirements as prenylation at position C-6 or C-8 and OH at positions C-5, 7, and 4′ are key to the antibacterial activity. The combination of 11 or 12 with commercial antibiotics synergistically enhanced the antibacterial activity of vancomycin, ciprofloxacin, and methicillin in a factor of 10 to 100 times against drug-resistant bacteria. Compound 11 combined with ciprofloxacin was able to decrease the levels of ROS generated by ciprofloxacin. According to docking results of S enantiomer of 11 with ATP-binding cassette transporter showed the most favorable binding energy; however, more studies are needed to support this result.     

Design,Synthesis, Antibacterial,Antifungal and Anticancer Evaluations of Novel β-Pinene Quaternary Ammonium Salts

β-pinene is a monoterpene isolated from turpentine oil and numerous other plants’ essential oils, which has a broad spectrum of biological activities. In the current work, six novel β-pinene quaternary ammonium (β-PQA) salts were synthesized and evaluated in vitro for their antifungal, antibacterial and anticancer activities. The in vitro assay results revealed that compounds 4a and 4b presented remarkable antimicrobial activity against the tested fungi and bacteria. In particular, compound 4a showed excellent activities against F. oxysporum f.sp. niveum, P. nicotianae var.nicotianae, R. solani, D. pinea and Fusicoccumaesculi, with EC₅₀ values of 4.50, 10.92, 9.45, 10.82 and 6.34 μg/mL, respectively. Moreover, compound 4a showed the best antibacterial action against E. coli, P. aeruginosa, S. aureus and B. subtilis, with MIC at 2.5, 0.625, 1.25 and 1.25 μg/mL, respectively. The anticancer activity results demonstrated that compounds 4a, 4b, 4c and 4f exhibited remarkable activity against HCT-116 and MCF-7 cell lines, with IC₅₀ values ranged from 1.10 to 25.54 μM. Notably, the compound 4c displayed the strongest cytotoxicity against HCT-116 and MCF-7 cell lines, with the IC₅₀ values of 1.10 and 2.46 μM, respectively. Furthermore, preliminary antimicrobial mechanistic studies revealed that compound 4a might cause mycelium abnormalities of microbial, cell membrane permeability changes and inhibition of the activity of ATP. Altogether, these findings open interesting perspectives to the application of β-PQA salts as a novel leading structure for the development of effective antimicrobial and anticancer agents.     

Synthesis,characterization, electrochemical behavior,thermal study and antibacterial/antifungal properties of some new zinc(II) coordination compounds

A novel symmetrical Schiff base ligand was prepared by condensation reaction of 2,2-dimethyl-1.3-diaminopropane and (E)3-(2nitrophenyl)acrylaldehyde. The ligand and its Zn(II) coordination compounds were well characterized by the elemental analysis, FTIR, ¹H, ¹³C NMR, UV–vis spectra and molar conductance. Thermal behaviors of all compounds were investigated from the room temperature to 600 °C with a heating rate of 10 °C/min. Furthermore some decomposition thermo-kinetic parameters were evaluated by Coats–Redfern equation at each decomposition step. Electrochemical properties of ligand and its complexes were studied by cyclic voltammetry technique. Also antibacterial/antifungal activities of the ligand and its complexes were tested against three Gram-negative bacteria Escherichia coli (ATCC 25922), Salmonella spp. and Pseudomonas aeruginosa (ATCC 9027) and two Gram-positive bacteria Staphylococcus aureus (ATCC 6538) and Corynebacterium renale and also three fungi (Aspergillus niger, Penicillium chrysogenum and Candida albicans). The results exhibited suitable antibacterial/antifungal properties for ligand and Zn(II) complexes. The study has shown that the complexation of ligand to zinc center lead to enhancement of antibacterial/antifungal activity.     

Evaluation of antithrombogenic and antibacterial activities of a graphite oxide/heparin-benzalkonium chloride composite

A graphite oxide (GO)/heparin-benzalkonium chloride (C12) composite was synthesized. The composite was characterized by X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). XRD data showed that spacing between layers of GO increased from 0.59 to 3.256 nm. This enlarged layer spacing suggested that heparin-C12 complex intercalated completely in between layers of GO. FTIR also confirmed intercalation of heparin-C12 complex into GO gallery. In vitro release rate of heparin from GO-heparin-C12 was monitored for 30 days. Heparin released at a very fast rate from the composite matrix in the first day. The release slowed down significantly after the first day and continued for 30 days. In addition, antibacterial activity of the composite against Escherichia coli (E. coli) and Staphlococcus aureus (S. aureus) was evaluated using zone of inhibition and colony count assays. Both GO-heparin-C12 and GO-C12 clearly showed antibacterial activity against E. coli and S. aureus while GO alone has a relatively low activity against S. aureus and almost no effect on E. coli.     

Investigation of antibacterial activity and related mechanism of a ruthenium(II) polypyridyl complex

Metal based drug represents a novel group of antimicrobial agents with potential application for the control of bacterial and fungal infections. In this study, we fabricate ruthenium(II) complex containing the polypyridyl ligands, namely [Ru(phen)₂(tip)] (ClO₄)₂ (RuTh) and carefully investigate its antibacterial activities against both the Gram-negative (G −) bacteria Escherichia coli (E. coli) and the Gram-positive (G +) bacteria Staphylococcus aureus (S. aureus). The RuTh is more toxic to S. aureus than that to E. coli. The antibacterial effects of RuTh are further investigated, revealing specific mechanisms. The results demonstrate that RuTh functions as a bactericide against the E. coli and S. aureus through disrupting bacterial cell wall integrity and its cellular components.     

PG-2, a Potent AMP against Pathogenic Microbial Strains,from Potato (Solanum tuberosum L cv. Gogu Valley) Tubers Not Cytotoxic against Human Cells

In an earlier study, we isolated potamin-1 (PT-1), a 5.6-kDa trypsin-chymotrypsin protease inhibitor, from the tubers of a potato strain (Solanum tuberosum L cv. Gogu Valley). We established that PT-1 strongly inhibits pathogenic microbial strains, but not human bacterial strains, and that its sequence shows 62% homology with a serine protease inhibitor. In the present study, we isolated an antifungal and antibacterial peptide with no cytotoxicity from tubers of the same potato strain. The peptide (peptide-G2, PG-2) was isolated using salt-extraction, ultrafiltration and reverse-phase high performance liquid chromatography (RP-HPLC). Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF/MS) showed the protein to have a molecular mass of 3228.5 Da, while automated Edman degradation showed the N-terminal sequence of PG-2 to be LVKDNPLDISPKQVQALCTDLVIRCMCCC-. PG-2 exhibited antimicrobial activity against Candida albicans, a human pathogenic yeast strain, and Clavibacter michiganensis subsp. michiganensis, a plant late blight strain. PG-2 also showed antibacterial activity against Staphylococcus aureus, but did not lyse human red blood cells and was thermostable. Overall, these results suggest PG-2 may be a good candidate to serve as a natural antimicrobial agent, agricultural pesticide and/or food additive.     

Comparative Antimicrobial Activity of Hp404 Peptide and Its Analogs against Acinetobacter baumannii

An amphipathic α-helical peptide, Hp1404, was isolated from the venomous gland of the scorpion Heterometrus petersii. Hp1404 exhibits antimicrobial activity against methicillin-resistant Staphylococcus aureus but is cytotoxic. In this study, we designed antimicrobial peptides by substituting amino acids at the 14 C-terminal residues of Hp1404 to reduce toxicity and improve antibacterial activity. The analog peptides, which had an amphipathic α-helical structure, were active against gram-positive and gram-negative bacteria, particularly multidrug-resistant Acinetobacter baumannii, and showed lower cytotoxicity than Hp1404. N-phenyl-1-naphthylamine uptake and DisC₃-5 assays demonstrated that the peptides kill bacteria by effectively permeating the outer and cytoplasmic membranes. Additionally, the analog peptides inhibited biofilm formation largely than Hp1404 at low concentrations. These results suggest that the analog peptides of Hp1404 can be used as therapeutic agents against A. baumannii infection.     

Synthesis and biological activities of 3-polyamino-5β-cholane-7α,24-diols

A series of 3-polyaminochenodeoxycholic acid derivatives were synthesized and their in vitro antimicrobial and antifungal activities were assessed. The antimicrobial activity was evaluated against Gram-positive and Gram-negative bacteria, and the antifungal activity was assessed against two strains Candida albicans (ATCC MYA-1003) and Aspergillus fumigatus (ATCC 16424). The introduction of an amine group to steroid was accomplished by reductive amination of 3-oxosteroid 9 with Boc-spermidine and Boc-spermine, in the presence of NaBH(OAc)₃. This afforded a high yield of 3-polyaminosteroids of 10–13. The 3β-sperminyl-5β-cholane 6 showed the highest antimicrobial activity against Streptococcus pyogenes 308A, Staphylococcus aureus 503, Escherichia coli DC2 and Pseudomonas aeruginosa 9027 with a MIC value of 3.13 μg/mL.     

Comparative Study of the Micellar and Antimicrobial Activity of Gemini-Conventional Surfactants in Pure and Mixed Micelles

We have carried out mixed micellization of pentanediyl-α,ω-bis(dimethyl cetylammonium bromide) (G5) with conventional cationic cetylpyridinium chloride (CPC) and nonionic polyoxyethylene (20) cetyl ether (C16E20) in aqueous media and explored their antimicrobial activity in single and binary systems against Escherichia coli (E.coli), Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus). The compounds tested showed excellent antibacterial activity: 0.76–3.38 g/l minimum inhibitory concentration (MIC) and were more active against gram +ve bacteria. For surfactant mixtures G5-C16E20 > G5-CPC, the ionic-nonionic binary surfactant showed greater antibacterial activity. The experimental results of this study may be profitably used to understand and predict the antibacterial activity of gemini-conventional surfactant systems and provide valuable information for selection of surfactant for microbiocidal action.     

Pereskia aculeata Muller (Cactaceae) Leaves: Chemical Composition and Biological Activities

The aims of this work were to study the chemical composition of the essential oil from the leaves of Pereskia aculeata and to evaluate some biological activities of three leaf extracts. The phenolic content, antioxidant activity, and in vitro antimicrobial and antifungal activities were determined. The methanol extract showed antioxidant activity (EC₅₀ 7.09 mg/mL) and high polyphenols content (15.04 ± 0.31 mg gallic acid equivalents (GAE)/g). The petroleum ether extract exhibited potent antibacterial activity against Escherichia coli, whereas the chloroform extract showed inhibitory activity against Bacillus cereus and Staphylococcus aureus. The petroleum ether and methanol extracts were more effective in inhibiting the growth of Aspergillus versicolor. The possible cytotoxicity of extracts on neuroblastoma SH-SY5Y cancer cell line and the influence on adenylate cyclase (ADCY) expression was also studied. P. aculeata chloroform extract showed antiproliferative activity with an IC₅₀ value of 262.83 µg/mL. Treatments of SH-SY5Y neuroblastoma cells with 100 µg/mL of methanol extract significantly reduced ADCY1 expression.     

Effect of Relative Arrangement of Cationic and Lipophilic Moieties on Hemolytic and Antibacterial Activities of PEGylated Polyacrylates

Synthetic amphiphilic polymers have been established as potentially efficient agents to combat widespread deadly infections involving antibiotic resistant superbugs. Incorporation of poly(ethylene glycol) (PEG) side chains into amphiphilic copolymers can reduce their hemolytic activity while maintaining high antibacterial activity. Our study found that the incorporation of PEG has substantially different effects on the hemolytic and antibacterial activities of copolymers depending on structural variations in the positions of cationic centers relative to hydrophobic groups. The PEG side chains dramatically reduced the hemolytic activities in copolymers with hydrophobic hexyl and cationic groups on the same repeating unit. However, in case of terpolymers with cationic and lipophilic groups placed on separate repeating units, the presence of PEG has significantly lower effect on hemolytic activities of these copolymers. PEGylated terpolymers displayed substantially lower activity against Staphylococcus aureus (S. aureus) than Escherichia coli (E. coli) suggesting the deterring effect of S. aureus’ peptidoglycan cell wall against the penetration of PEGylated polymers. Time-kill studies confirmed the bactericidal activity of these copolymers and a 5 log reduction in E. coli colony forming units was observed within 2 h of polymer treatment.     

Facile preparation and good performance of nano-Ag/metallocene polyethylene antibacterial coatings

Metallocene polyethylene/nano-silver coatings were prepared by a facile air-spray method on polymer films. Different from the prevailing strategy to endow polyethylene with antibacterial performance, we used metallocene polyethylene sol and nano-silver as a precursor to deposit coatings on polymers at a relatively low operating temperature. Antibacterial coatings with excellent mechanical properties, water resistance, and low silver release were achieved. The composite coatings were examined in terms of surface characteristics, mechanical properties, and antibacterial activity against two representative bacterial strains including Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The composite coatings exhibited favorable microstructure, good mechanical properties, and suitable crystallinity. The antimicrobial tests indicated that the fabricated composite coatings showed promising antibacterial activity against E. coli and S. aureus. Furthermore, Ag ions released by the composite coating after 30 days were under 1.2 ppb. These results indicated a promising prospect of the composite coating for wide antibacterial applications.     

Peptides from the Intestinal Tract of Breast Milk-Fed Infants Have Antimicrobial and Bifidogenic Activity

For bioactive milk peptides to be relevant to infant health, they must be released by gastrointestinal proteolysis and resist further proteolysis until they reach their site of activity. The intestinal tract is the likeliest site for most bioactivities, but it is currently unknown whether bioactive milk peptides are present therein. The purpose of the present study was to identify antimicrobial and bifidogenic peptides in the infant intestinal tract. Milk peptides were extracted from infant intestinal samples, and the activities of the bulk peptide extracts were determined by measuring growth of Escherichia coli, Staphylococcus aureus, and Bifidobacterium longum spp. infantis after incubation with serial dilutions. The peptide profiles of active and inactive samples were determined by peptidomics analysis and compared to identify candidate peptides for bioactivity testing. We extracted peptides from 29 intestinal samples collected from 16 infants. Five samples had antimicrobial activity against S. aureus and six samples had bifidogenic activity for B. infantis. We narrowed down a list of 6645 milk peptides to 11 candidate peptides for synthesis, of which 6 fully inhibited E. coli and S. aureus growth at concentrations of 2500 and 3000 µg/mL. This study provides evidence for the potential bioactivity of milk peptides in the infant intestinal tract.     

Synthesis and Biological Evaluation of 2-Aminobenzamide Derivatives as Antimicrobial Agents: Opening/Closing Pharmacophore Site

A series of new 2-aminobenzamide derivatives (1–10) has been synthesized in good to excellent yields by adopting both conventional and/or a time-efficient microwave assisted methodologies starting from isatoic anhydride (ISA) and characterized on the basis of their physical, spectral and microanalytical data. Selected compounds of this series were then tested against various bacterial (Bacillus subtilis (RCMB 000107) and Staphylococcus aureus (RCMB 000106). Pseudomonas aeruginosa (RCMB 000102) and Escherichia coli (RCMB 000103) and fungal strains (Saccharomyces cerevisiae (RCMB 006002), Aspergillus fumigatus (RCMB 002003) and Candida albicans (RCMB 005002) to explore their potential as antimicrobial agents. Compound 5 was found to be the most active compound among those tested, which showed excellent antifungal activity against Aspergillus fumigatus (RCMB 002003) more potent than standard Clotrimazole, and moderate to good antibacterial and antifungal activity against most of the other strains of bacteria and fungi. Furthermore, potential pharmacophore sites were identified and their activity was related with the structures in the solution.