Total Synthesis and Biological Evaluation of the Antibiotic Lysocin E and Its Enantiomeric,Epimeric, and N‐Demethylated Analogues

Lysocin E, a macrocyclic peptide, exhibits potent antibacterial activity against methicillin‐resistant Staphylococcus aureus (MRSA) through a novel mechanism. The first total synthesis of lysocin E was achieved by applying a full solid‐phase strategy. The developed approach also provides rapid access to the enantiomeric, epimeric, and N‐demethylated analogues of lysocin E. Significantly, the antibacterial activity of the unnatural enantiomer was comparable to that of the natural isomer, suggesting the absence of chiral recognition in its mode of action.     

Synthesis and Antibacterial Activities of 2‐(1‐Aryl‐5‐Methyl‐1,2,3‐triazol‐4‐yl)‐1,3,4‐Oxadiazole Derivatives

Eighteen novel 2‐(1‐aryl‐5‐methyl‐1,2,3‐triazol‐4‐yl)‐1,3,4‐oxadiazole derivatives and two acylhydrazone intermediate compounds were synthesized by various pathways starting from 1‐aryl‐5‐methyl‐1,2,3‐triazol‐4‐formhydrazide ( 1 ). All products were identified by spectroscopic analysis, and 2‐(1‐aryl‐5‐methyl‐1,2,3‐triazol‐4‐yl)‐5‐benzalthio‐1,3,4‐oxadiazole was further validated by X‐ray crystallography. Results from primary antibacterial activity tests indicated that most of the compounds were effective against E. coli, P. aeruginosa, B. subtilis and S. aureus.     

Synthesis,Characterization, and In Vitro Antibacterial Activities of Macromolecules Derived from Bis‐Chalcone

We investigated the antibacterial activity of some new macromolecules such as bis‐pyrazoline, bis‐pyrazole, bis‐pyrimidines prepared from the reaction of bis‐chalcone with thiosemicarbazide/phenyl hydrazine/guanidine hydrochloride/thiourea. All the macromolecules have been characterized by IR, ¹H NMR, ¹³C NMR, mass and elemental analyses. The antibacterial activity of these compounds was first tested in vitro by the disc diffusion assay against two Gram‐positive and two Gram‐negative bacteria, and then the minimum inhibitory concentration was determined with the reference to standard drug chloramphenicol. The results showed that pyrazoline derivative showed better antibacterial activity on S. typhimurium and E. coli than the reference drug chloramphenicol.     

Synthesis and Antibacterial Activity of s‐Triazoles,s‐Triazolo[3,4‐b]‐1,3,4‐thiadiazines and s‐Triazolo[3,4‐b]‐1,3,4‐thiadiazoles of 5‐Methylisoxazole

The condensation of 4‐amino‐5‐mercapto‐3‐(5‐methylisoxazol‐3‐yl)‐1,2,4‐triazole with substituted phenacyl bromide, aldehydes, p‐bromophenylisothiocyanate, aromatic carboxylic acids and oxalic acid, is described. The antibacterial activity of representative compounds was evaluated.     

微量热研究几种新型吡啶酰胺希夫碱对大肠杆菌的抑制作用

用微量热研究一系列新型吡啶酰胺希夫碱对大肠杆菌的抑制作用, 不同的吡啶酰胺希夫碱衍生物对大肠杆菌生长的抑制作用不同. 通过热动力学模型计算得到生长速率常数(k)和抑制率(I), 我们获得了吡啶酰胺希夫碱衍生物的抗菌作用效果. 通过药物作用于细菌处于生长对数期的实验发现, 有两种化合物(F和G)对大肠杆菌生长有非常好的抑制作用, 他们的半抑制浓度(IC50)分别是0. 106 和0. 113 g/L, 但是药物对大肠杆菌的无氧发酵过程抑制作用比较差. 通过进一步分析药物结构与药物半抑制浓度, 我们发现: 希夫碱衍生物的亲水性对其抗菌活性有很大的影响, 这主要是由细菌的细胞膜结构不同所致. 对希夫碱及其碱衍物的结构与抗菌活性关系进行了初步探讨, 它们对大肠杆菌的抗菌活性顺序为: F＞G＞C＞D＞E＞B＞A.     

Synthesis,characterization and in vitro biological activity of new zinc(II) complexes of the nonsteroidal anti‐inflammatory drug sulindac and nitrogen‐donor ligands

Metal carboxylate compounds with nitrogen‐ and/or oxygen‐donor ligands with various carboxylate coordination modes, monodentate, bidentate and bridging bidentate, have been shown to be important from biological and chemical aspects. Five zinc ion binary compounds, diaqua‐bis‐(2‐((E )‐5‐fluoro‐2‐methyl‐1‐(4‐(methylsulfinyl)benzylidene)‐1H –inden‐3‐yl)acetato)zinc(II) ( 1 ), aqua‐bis‐(2‐((E )‐5‐fluoro‐2‐methyl‐1‐(4‐(methylsulfinyl)benzylidene)‐1H –inden‐3‐yl)acetato)pyridin‐2‐aminezinc(II) ( 2 ), (2‐((E )‐5‐fluoro‐2‐methyl‐1‐(4‐(methylsulfinyl)benzylidene)‐1H –inden‐3‐yl)acetato) pyridin‐2‐ylmethanaminezinc(II) (2‐((E )‐5‐fluoro‐2‐methyl‐1‐(4‐(methylsulfinyl)benzylidene)‐1H –inden‐3‐yl)acetate) ( 3 ), bis‐(2‐((E )‐5‐fluoro‐2‐methyl‐1‐(4‐(methylsulfinyl)benzylidene)‐1H –inden‐3‐yl)acetato)‐1,10‐phenanthrolinezinc(II) ( 4 ) and bis‐(2‐((E )‐5‐fluoro‐2‐methyl‐1‐(4‐(methylsulfinyl)benzylidene)‐1H –inden‐3‐yl)acetato)‐1,10‐phenanthrolinezinc(II) ( 5 ), have been prepared and fully characterized. In addition, the complexes were evaluated for their antibacterial activity using the in vitro agar diffusion method against two Gram‐positive (Staphylococcus epidermidis , Staphylococcus aureus ) and two Gram‐negative (Bordetella , Escherichia coli ) bacteria and yeast species (Saccharomyces and Candida ). Complex 5 showed reasonable activity against yeast. All compounds showed greater antibacterial activity against Gram‐positive than Gram‐negative bacteria. Results indicated that the efficiency of complex 5 in preventing the formation of β‐hematin was 67.6%. The efficiency of chloroquine as a standard drug was reported as 93%. Furthermore, the phosphatase activity of the Zn(II) complexes was studied and results indicated an effect of the zinc complexes on phosphatase activity.     

Synthesis and Antibacterial Activity of Some New 2,5‐Disubstituted‐1,3,4‐oxadiazole Derivatives

Synthesis of some new oxadiazole derivatives starting from 1,2,3-benzo[d]triazole-1-acetic hydrazide (1) is described. The target compounds 2-(N-substituted-aminocarbonylmethylthio)-5-(1,2,3-benzo[d]triazol-1-ylmethyl)- 1,3,4-oxadiazole (4a—4i) and 2-[2-(N-substituted-aminocarbonyl)ethylthio]-5-(1,2,3-benzo[d]triazol-1-ylmethyl)- 1,3,4-oxadiazole (5a—5i) were obtained in good yields via cyclisation of 1 and subjected to antibacterial activity test against pathogenic bacteria. The halogen containing mono- and di-substituted derivatives showed excellent antibacterial activity compared to other analogues.     

Functionalization of Quinazolin‐4‐Ones Part 2#: Reactivity of 2‐Amino‐3, 4, 5, or 6‐Nitrobenzoic Acids with Triphenylphosphine Thiocyanate,Alkyl Isothiocyanates,and Further Derivatization Reactions

2‐amino‐3, 4, 5, or 6‐nitrobenzoic acids were reacted with PPh₃(SCN)₂ and alkyl isothiocyanates to give 5, 6, 7, or 8‐nitro‐2‐thioxo‐3‐substituted quinazolin‐4‐ones, respectively. The position of the nitro group was found to have significant influence on the outcome of the reactions. Similarly, the nature of the substituent at position 8 (NO₂, NH₂, NH(C═O)CH₃) in 8‐substituted‐2‐methylthio quinazolin‐4‐ones was also found to significantly influence their reactivity towards morpholine. A selection of the products were also tested for in vitro antibacterial activity but little activity was observed.     

Synthesis and antibacterial activities of water‐soluble methacrylate polymers containing quaternary ammonium compounds

New water‐soluble methacrylate polymers with pendant quaternary ammonium (QA) groups were synthesized and used as antibacterial materials. The polymers with pendant QA groups were obtained by the reaction of the alkyl halide groups of a previously synthesized functional methacrylate homopolymer with various tertiary alkyl amines containing 12‐, 14‐, or 16‐carbon alkyl chains. The structures of the functional polymer and the polymers with QA groups were confirmed with Fourier transform infrared and ¹H and ¹³C NMR. The degree of conversion of alkyl halides to QA sites in each polymer was determined by ¹H NMR to be over 90% in all cases. The number‐average molecular weight and polydispersity of the functional polymer were determined by size exclusion chromatography to be 32,500 g/mol and 2.25, respectively. All polymers were thermally stable up to 180 °C according to thermogravimetric analysis. The antibacterial activities of the polymers with pendant QA groups against Staphylococcus aureus and Escherichia coli were determined with broth‐dilution and spread‐plate methods. All the polymers showed excellent antibacterial activities in the range of 32–256 μg/mL. The antibacterial activity against S. aureus increased with an increase in the alkyl chain length for the ammonium groups, whereas the antibacterial activity against E. coli decreased with increasing alkyl chain length. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 5965–5973, 2006     

Zeolite‐Supported One‐Pot Synthesis of Bis‐azetidinones under Microwave Irradiation

In an attempt to synthesize antibacterial agents effective against gram‐positive and gram‐negative bacteria, the efficient synthesis of novel bis‐azetidinones ( 3a–j ) has been established. Thus, cycloaddition reaction of substituted bis‐imines with chloroacetylchloride under microwave irradiation in the presence of zeolite yielded bis‐azetidinones ( 3a–j ). Structures of the synthesized compounds have been elucidated on the basis of their elemental analysis and spectral data (IR, ¹H‐NMR, ¹³C‐NMR, and mass spectra). The synthesized bis‐azetidinones were screened for their antibacterial activity against five microorganisms: Bacillus subtilis, Proteus vulgaris, Staphylococcus aureus, Klebsiella pneumoniae, and Escherichia coli. They were found to exhibit good to moderate antibacterial activity.     

4‐Hydroxy‐3‐carboxycoumarin as an efficient building block for new ruthenium(II) complexes: synthesis,characterization, antibacterial,antioxidant and anti‐inflammatory activities

A new 4‐hydroxy‐3‐carboxycoumarin ligand and its ruthenium(II) complexes ( 1 – 5 ) have been synthesized, characterized and screened for their in vitro antibacterial activity against a range of Gram‐positive and Gram‐negative bacteria. In addition, compounds 1 – 5 were investigated for antioxidant activities using superoxide radical, 2,2‐diphenyl‐1‐picrylhydrazyl radical and hydroxyl radical scavenging assays, in which most of them displayed significant antioxidant activities. Furthermore, compounds 1 – 5 were evaluated for anti‐inflammatory activity using indirect haemolytic and lipoxygenase inhibition assays and revealed good activity. The new complexes were characterized using spectroscopic methods in addition to elemental analysis.     

Synthesis,Reactions and Antimicrobial Activity of Some New Indolyl‐1,3,4‐Oxadiazole,Triazole and Pyrazole Derivatives

Indole‐3‐carboxylic acid hydrazide 3 was prepared and was treated with aromatic aldehydes in ethanol to give the corresponding hydrazone derivatives 4–7 in good yields. The indole carbohydrazide was incorporated into the 3‐indolyloxadiazoles 8–11 and 18 , 3‐indolyltriazoles 13–17 and 35 , 3‐indolylpyrazole derivatives 19–23 and carbamate derivatives 26–27 . Furthermore, interaction of the carboazide 24 with hydrazine hydrate in refluxing toluene afforded the corresponding semicarbazide derivative 30 . The thiadiazine derivative 34 was also prepared. Some of these compounds were screened in vitro for their antibacterial and antifungal activity.     

A mixed‐ligand quinazoline‐based Ni(II) Schiff base complex: Synthesis,characterization, crystal structure,antimicrobial investigation and catalytic activity for the synthesis of 2H–indazolo[2,1‐b]phthalazine‐triones

A tridentate Schiff base ligand, (E)‐3‐((2‐hydroxy‐3‐methoxybenzylidene)amino)‐2‐methylquinazolin‐4(3H)‐one [HL], and its mixed‐ligand Ni(II) complex [Ni(L)(imi)], were synthesized and fully characterized using elemental analysis, FT‐IR, UV–Vis and ¹HNMR spectroscopy techniques. The structure of the synthesized ligand and complex was determined with single crystal X‐ray diffraction method. In the complex, a square planner geometry was observed around the Ni(II) central atom coordinated with the donor atoms of the Schiff base ligand and one nitrogen of imidazole group. In addition, the catalytic activity of the complex on the three‐component condensation of hydrazine hydrate with phthalic anhydride and dimedone to obtain 2H–indazolo[2,1‐b]phthalazine‐triones was investigated. Furthermore, in‐vitro antimicrobial studies were performed that indicated the great antibacterial activities of the Ni(II) complex against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa and Bacillus cereus bacteria.     

Antibacterial Drug Release Electrochemically Stimulated by the Presence of Bacterial Cells – Theranostic Approach

A modified electrode with bioaffinity to E. coli bacterial cells was used to detect bacteria presence on its surface and to produce an electrical signal triggering antibacterial drug release from another coupled electrode. The Sense‐and‐Treat system was realized in two different versions and suggested as the first step to future theranostic applications where bacteria presence results in automatic antibacterial treatment.     

N‐Phenyl‐substituted carbene precursors and their silver complexes: synthesis,characterization and antimicrobial activities

A series of unsymmetrically substituted N‐heterocyclic carbene (NHC) precursors ( 1a , 1b , 1c , 1d , 1e ) were synthesized from the reaction of N‐phenylbenzimidazole with various alkyl halides. These compounds were used to synthesize NHC–silver(I) complexes ( 2a , 2b , 2c , 2d , 2e ). The five new 1‐phenyl‐3‐alkylbenzimidazolium salts ( 1a , 1b , 1c , 1d , 1e ) and their NHC–silver complexes ( 2a , 2b , 2c , 2d , 2e ) were characterized by the ¹H NMR, ¹³C NMR and FT‐IR spectroscopic methods and elemental analysis techniques. Also, the two NHC–silver complexes 2b and 2c were characterized by single‐crystal X‐ray crystallography, which confirmed the linear C―Ag―Cl arrangements. The antibacterial activities of the NHC precursor and NHC–silver complexes were tested against three Gram‐positive bacterial strains (Bacillus subtilis, Listeria monocytogenes and Staphylococcus aureus) and three Gram‐negative bacterial strains (Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa) using the microdilution broth method. The NHC–silver complexes showed higher antibacterial activity than the NHC precursors. In addition, silver complexes 2a , 2b , 2c , 2d showed high antibacterial activity against the Gram‐positive bacteria L. monocytogenes and S. aureus compared to the standard, tetracycline. Copyright © 2014 John Wiley & Sons, Ltd.     

Full polysaccharide chitosan‐CMC membrane and silver nanocomposite: synthesis,characterization, and antibacterial behaviors

Chitosan‐carboxymethyl cellulose (CMC) full polysaccharide membrane was prepared by cross‐linking of chitosan with CMC dialdehyde and subsequent reductive amination. CMC dialdehyde molecule was prepared by periodate oxidation of CMC and then applied as a cross‐linking agent to form a new membrane network. The properties of oxidized CMC were investigated by various methods such as Fourier transform infrared (FT‐IR) spectroscopy, ¹H NMR spectroscopy, and viscosity test. Then, novel chitosan‐CMC silver nanocomposite was prepared using chitosan‐CMC as a carrier. The structure of the chitosan‐CMC membrane and the silver nanocomposite were confirmed by FT‐IR spectroscopy, scanning electron microscopy (SEM), transmission electron microscopy (TEM), and thermogravimetric analysis (TGA). TEM images indicate that the chitosan‐CMC nanocomposite comprises silver nanoparticles with diameters in the range of about 5–20 nm. The antibacterial studies of the nanocomposite were also evaluated. The chitosan‐CMC silver nanocomposite demonstrates good antibacterial activity against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli. Copyright © 2016 John Wiley & Sons, Ltd.     

Hybrid 4‐Aminoquinoline‐1,3,5‐triazine Derivatives: Design,Synthesis, Characterization,and Antibacterial Evaluation

A series of novel 4‐aminoquinoline 1,3,5‐triazine derivatives were synthesized and characterized by FTIR, ¹H‐NMR, ¹³C‐NMR, MS, and elemental analysis. The antibacterial activities of synthesized compounds were tested against three Gram‐positive bacteria, namely Bacillus subtilis (NCIM‐2063), Bacillus cereus (NCIM‐2156), and Staphylococcus aureus (NCIM‐2079), and four Gram‐negative bacteria, namely Proteus vulgaris (NCIM‐2027), Proteus mirabilis (NCIM‐2241), Escherichia coli (NCIM‐2065), and Pseudomonas aeruginosa (NCIM‐2036), using ciprofloxacin as reference standard drug. Results showed compound 9a and 9e as potent antibacterial agents against all bacterial strains except Bacillus cereus (NCIM‐2156). Copyright © 2014 HeteroCorporation     

Thermo‐Switchable Antibacterial Activity

A copolymer system of 2‐aminoethyl methacrylate and N‐isopropylacrylamide comprises novel properties: changes in conformation and hydrophilicity upon heating influence the antibacterial activity and result in a switchable biocidal effect. The copolymers are characterized via NMR, MALDI‐ToF MS, phase transition behavior, and antibacterial tests with E. coli or B. subtilis. MIC and MBC are determined using standard dilution methods, temperature‐dependence via incubation at different temperatures and cytotoxicity by MTT tests. The copolymers exhibit lower MIC in globule than coil conformation, crosslinking on cotton results in non‐leaching materials with better antibacterial activity above than below the phase‐transition point.

     

Novel arylpyridine‐based 1,3,4‐oxadiazoles: Synthesis,antibacterial, and anti‐inflammatory evaluation

In view of developing novel bioactive compounds, a series of 2‐(5‐[2‐methyl‐6‐arylpyridin‐3‐yl]‐1,3,4‐oxadiazol‐2‐ylthio)‐1‐arylethanones (6a–n) were designed and synthesized in good yield. Novel compounds were evaluated for their antibacterial and anti‐inflammatory activities. All synthesized compounds were screened for their antibacterial activity against Staphylococcus aureus, Bascillus subtilis, Eschericia coli, and Pseudomonas aeruginosa strains. Compounds 6a , 6b , 6c , 6h , and 6i displayed the highest antibacterial activity with minimal inhibitory concentration (MIC) values ranging from 6.25–12.5 μg/mL in comparison with the standard Ciprofloxacin. The results of anti‐inflammatory activity of carrageenan‐induced footpad edema assay indicated that tested compounds exhibited remarkable anti‐inflammatory activity with percentage of inhibition of 63.9–70.1% (potency 96.8–106.20% of indomethacin activity) after 3 hr. Particularly, 6c – e and 6j – l were found to be excellent inhibitors of inflammation, with potential higher than that of the standard, Indomethacin.     

Organometallic based biologically active compounds: synthesis of mono‐ and di‐ethanolamine derived ferrocenes with antibacterial,antifungal and cytotoxic properties

Condensation reactions of 1,1′‐diacetylferrocene with ethanolamine were studied. The obtained compounds were further investigated for their ligation and biological properties with Co(II), Cu(II), Ni(II) and Zn(II) metal ions. The synthesized compounds were characterized by their physical, spectral and analytical properties and screened for their antibacterial properties against pathogenic bacterial strains, e.g. Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus and Salmonella typhi and for antifungal activity against Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glaberata using the agar‐well diffusion method. All the compounds have shown good antibacterial and antifungal activity, which increased on coordination with the metal ions, thus introducing a potential class of organometallic‐based antibacterial and antifungal agents. Brine shrimp bioassay was also carried out for in vitro cytotoxic properties against Artemia salina. Copyright © 2007 John Wiley & Sons, Ltd.