One-pot synthesis, antibacterial and antifungal activities of novel 2,5-disubstituted-1,3,4-oxadiazoles

A series of novel 2,5-disubstituted-1,3,4-oxadiazoles have been synthesized from long-chain alkanoic and alkenoic acids. The structures of these compounds have been elucidated by elemental and spectral （IR, ^1H NMR, ^13C NMR, MS） analysis. Furthermore, compounds were screened for in vitro antibacterial activity against the representative panel of two Gram-positive and two Gram- negative bacteria. All the synthesized compounds were also tested for their inhibitory action against five strains of fungus. The various compounds show potent inhibitory action against test organisms. 2007 Abdul Rauf. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.     

A straightforward approach to 2-azetidinones from imines and carboxylic acids using dimethyl sulfoxide and acetic anhydride

The direct synthesis of 2-azetidinones from imines and carboxylic acids under mild conditions is developed. Dimethyl sulfoxide (DMSO) can be activated by acetic anhydride and the resulting active species is used for the in situ generation of ketenes from carboxylic acids. This method is cheap, simple, convenient, and efficient and the products are easily isolated.     

Preparation of 2-azetidinones by cyclocondensation of carboxylic acids and imines via diphosphorustetraiodide

One-pot mild synthesis of 2-azetidinones was carried out by the reaction of imines and carboxylic acids in dry dichloromethane at room temperature using diphosphorus tetraiodide. It was also applied for synthesis of 3-spiro-2-azetidinones. The synthesized compounds were characterized by analytical and spectral (infrared, ¹H NMR, ¹³C NMR, and elemental analysis) data.     

Synthesis and antimicrobial activity of Schiff bases and 2-azetidinones derived from quinazolin-4(3H)-one

A series of 2-oxo-azetidinyl-quinazolin-4(3H)-ones 5a–k have been synthesized from Schiff bases 4a–k. Schiff bases were synthesized by the condensation reaction of compound 3 with substituted aromatic aldehydes. The benzoxazinone 2 was prepared by the cyclization reaction of acid chloride 1 with 5-bromo anthranilic acid. Further reaction of benzoxazinone 2 with hydrazine hydrate yielded compound 3. The structures of the synthesized compounds were elucidated on the basis of elemental analyses as well as IR and NMR spectral data. Schiff bases 4a–k and 2-azetidinones 5a–k were screened for antibacterial and antifungal activities in vitro. Compounds having chloro and methoxy groups exhibited good antimicrobial activity.     

Synthesis,in vitro antibacterial and antifungal evaluation of novel 1,3,4-oxadiazole thioether derivatives bearing the 6-fluoroquinazolinylpiperidinyl moiety

A series of structurally novel 1,3,4-oxadiazole thioether derivatives(6a-6z) containing a 6-fluoroquinazolinylpiperidinyl moiety were designed and synthesized using pharmacophore hybrid approach,and their structures were fully characterized by ^1H NMR,¹³C NMR and HRMS spectra.Among them,the structure of compound 6 d was further corroborated via single-crystal X-ray diffraction analysis.In vitro antibacterial bioassays showed that compounds 6 a,6 g,6 u and 6 v possessed EC₅₀ values of 30.4,30.6,27.5 and 26.0 μg/mL against phytopathogenic bacterium Xanthomonas oryzae pv.oryzae,respectively,which were significantly superior to that of commercially-available bactericide Bismerthiazol(85.1 μg/mL).Moreover,in vitro antifungal bioassays indicated that seven compounds demonstrated broad-spectrum fungicidal acitivties against six types of phytopathogenic fungi at 50 μg/mL.The present work showed the potential of 1,3,4-oxadiazole thioether derivatives carrying a 6-fluoroquinazolinylpiperidinyl moiety as effective antimicrobial agents for crop protection,deserving further investigations in the future.     

Design,synthesis,in vitro evaluation of tetrahydropyrimidine-isatin hybrids as potential antibacterial,antifungal and anti-tubercular agents

A series of 5-substitued-3-(5-(4-(furan-2-yl)-6-methyl-2-oxo/thioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-1,3,4-thiadiazol-2- ylimino)indolin-2-one derivatives were synthesized,characterized and were screened for anti-bacterial,anti-fungal and antitubercular activity.     

Indole-3-acetic acid based tunable hydrogels for antibacterial,antifungal and antioxidant applications

Indole-3-acetic acid (IAA) based biopolymeric hydrogels with tunable anti-oxidant and anti-fungal character has been synthesized via condensation polymerization as pH-sensitive hydrophilic material.The present study focused on the synthesis of antifungal heterocyclic hydrogel using citric acid (CA), indole-3-acetic acid (IAA) and ethylene glycol (EG) by condensation polymerization. The hydrogels revealed a pH-sensitive swelling behavior, with increased swelling in acidic media, which in turn has decreased the swelling in the basic media.The hydrogel samples were tested for antifungal activity against Aspergillus fumigates, Rhizopusoryzae and Candida albicans at different concentrations (500, 1000, 1500, 2000 μg/well). Ketoconazole was used as positive control and DMSO as negative control for antifungal activity. Fungi were increasingly identified as major pathogens in various infections. Hydrogels with antifungal properties may constitute an important restriction to fungal infections. The biopolymeric hydrogels were characterized by Fourier transform infrared (FT-IR) spectroscopy, ¹H-NMR,¹³C-NMR, TGA, DSC followed by scanning electron microscopy (SEM). The increased antifungal activity was monitored in equimolar composition more than that of other compositions. The antioxidant activity of ICE with DPPH and NO radicals has been compared with rutin. Such antifungal hydrogels with antioxidant properties is recommended for medical applications such as bandages, catheters, drains and tubes to prevent infection.     

An efficient formal synthesis of (S)-dapoxetine from enantiopure 3-hydroxy azetidin-2-one

An efficient formal synthesis of S-(+) dapoxetine starting from 3-hydroxy azetidin-2-one is described. The intermediate (S)-3-(dimethyl amino)-3-phenylpropan-1-ol was synthesized in enantiopure form starting with 3-hydroxy azetidin-2-one in seven steps.     

Synthesis of New N-Sulfonyl Monocyclic β-Lactams and the Investigation of Their Antibacterial Activities

New monocyclic β-lactams 4–6 were synthesized by a ketene-imine [2+2] cycloaddition reaction. The prepared monocyclic β-lactams 4–6 were cleaved by ceric ammonium nitrate (CAN) to give NH-β-lactams 7–9. The NH-β-lactams were converted to N-sulfonyl β-lactams 10–21 by treatment with four different sulfonyl chlorides in the presence of Et₃N and 4-N,N-dimethylaminopyridine (DMAP). Some of these monocyclic β-lactams were active against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Design,synthesis and antifungal activities in vitro of novel tetralin compounds

Novel chiral tetralin compounds were designed and synthesized, and their antifungal activities in vitro were tested. The results showed that all of target compounds had potent antifungal activities, and were stronger than that of control compounds tetrahydroisoquinolines. The binding model of lead molecules in the active site of CYP51 of Candida albicans showed that lead compound specifically interacted with the amino acids residues in the active site, without binding with the heme of CYP51, which was different from azole antifungal drugs. The present study might afford a novel lead molecule to develop non-azole CYP51 inhihitars of fungi.     

Synthesis of neamine-carboline conjugates for RNA binding and their antibacterial activities

Three types of neamine-β-carboline conjugates were synthesized in good yields by the coupling of neamine and β-carboline-3-carboxylic acids using aliphatic diamine as a linker. The binding properties of these conjugates to 16S rRNA and 18S rRNA were evaluated by surface plasmon resonance (SPR), showing that some conjugates had stronger binding affinities than neamine. In vitro antimicrobial activities were also evaluated and the results showed that some synthetic compounds exhibited better antibacterial activities than neamine. The preliminary structure-activity relationship was discussed. The present experimental data demonstrated that synthetic neamine-carboline conjugates might hold the potential as new antibiotics.     

Asymmetric synthesis and biological evaluation of 3-nitro-2H-chromenes as potential antibacterial agents

A one-pot organocatalytic domino Henry/Michael/dehydration sequence of various salicylaldehyde derivatives with nitromethane as a dual-nucleophile is disclosed. This straightforward strategy assembles the optically active (R)-2-alkyl 3-nitro-2H-chromenes with good to excellent enantioselectivities (up to 93% ee) and a broad substrate scope. Preliminary in vitro antibacterial evaluation revealed most of the chiral 3-nitro-2H-chromene derivatives exhibit antibacterial activities against four Gram-positive bacteria. Compound 3p with two bromine substituents on the core scaffold was shown to be the best antibacterial agent in the series against S. aureus, B. subtilis and Bacillus cereus with minimal bactericidal concentration (MBC) values of 4?μg/mL, and against Staphylococcus epidermidis with a MBC value of 8?μg/mL.     

Benzylidene/2-aminobenzylidene hydrazides: Synthesis,characterization and in vitro antimicrobial evaluation

In this study a series of new mannich bases were synthesized and characterized by elemental and spectral (IR, ¹H NMR, ¹³C NMR) studies. All the synthesized compounds were evaluated for their antimicrobial activity by broth dilution method against two Gram negative strains (Escherichia coli and Pseudomonas aeruginosa), two Gram positive strains (Bacillus subtilis and Staphylococcus aureus) and fungal strain (Candida albicans and Aspergillus niger). Preliminary pharmacological evaluation revealed that the compounds (3f, 3i, 3j, and 3k) showed good activity against these strains. The result demonstrates the potential and importance of developing new mannich bases which would be effective against resistant bacterial and fungal strain.     

Antibacterial and antifungal activity of metal(II) complexes of acylhydrazones of 3-isatin and 3-(N-methyl)isatin

Cobalt(II), nickel(II), copper(II) and zinc(II) complexes of 2-thiophenecarbonyl hydrazone of 3-isatin (H₂L¹) and 2-furoic hydrazones of 3-isatin (H₂L²) and 3-(N-methyl)isatin (HL³), with general composition [M(L)₂] · nX, where X is ethanol or/and water, were synthesised and characterised. The molecular structure of HL³ showed that it crystallised in the keto form, which is also the more abundant tautomer for the three hydrazone ligands in solution. The three ligands behave as κ²-O,N donors in the cobalt(II) and zinc(II) complexes. The X-ray crystal structure of pseudotetrahedral [Zn(HL¹)₂] · 1.75MeOH confirmed the O,N coordination mode of the two monodeprotonated ligands in their keto forms. Secondary interactions of zinc ions with the O atoms of each isatin keto residue provoke a substantial distortion towards a square pyramidal form. The interaction of the isatin keto residues is stronger in the three nickel(II) complexes where the three acylhydrazones can be considered as κ³-O,N,O donors.     

Synthesis and antifungal activities of novel trifluoroethane derivatives with coumarin,indole and thiophene

A series of novel 1-(β-coumarinyl)-1-(β-indolyl)-1-(α-thiophenyl)trifluoroethane derivatives 5aaa-5hdb were prepared by one-pot reaction from 3-(trifluoroacetyl)coumarin with indole and α-substituted thiophene. Their structures were confirmed by ¹H NMR, ¹³C NMR, ¹⁹F NMR, HRMS and X-ray single crystal diffraction, and their antifungal activities against F. moniliforme, F. graminearum, F. oxysporum, R. solani and P. nicotianae were evaluated. The title compounds displayed significant to moderate in vitro antifungal activity when compared to the standard drug triadimefon. Among the synthesized compounds, compound 5bfa showed the highest inhibitor rate of 83.5 % at 0.500 mg/mL against R. solani, while compound 5ada displayed the highest inhibitor rate of 73.3 % at 0.500 mg/mL against F. graminearum.     

Ionic liquid-supported chiral saldach with tunable hydrogen bonding: synthesis,metalation with Fe(III) and in vitro antimicrobial susceptibility

New water-soluble methylimidazolium ionic liquids (MIILs) bearing N,N′-bis-(salicylidene)-R,R-1,2-diaminocyclohexane (saldach) scaffold, H₂(R¹)₂saldach(2-MeIm⁺X⁻)₂ (4a: R¹=H, X=Cl^–; 4b: R¹=H, X=PF₆^–; 4c: R¹=H, X=BF₄^–; 4d: R¹=ⁱPr, X=Cl^–; 4e: R¹=ⁱPr, X=PF₆^–; 4f: R¹=ⁱPr, X=BF₄^–), and their Fe(III) complexes have been synthesized and structurally characterized as well as their profile of antimicrobial susceptibility was identified. The new saldach-supported MIILs demonstrated a distinctly enhanced biocidal effect toward methicillin resistant Staphylococcus aureus (MRSA) and multidrug-resistant Escherichia coli (MDREC). Compound 4d is the most potent antibacterial agent and could inhibit the growth of all micro-organisms, except A. flavus, more effectively than standard antibiotics.     

Theoretical study of the conformational and electrostatic properties of C4-monosubstituted 2-azetidinones

The conformational preferences and electrostatic properties of 2-azetidinone, 4-(S)-methoxycarbonyl-2-azetidinone and 4-(R)-methyl-2-azetidinone have been studied in gas-phase, aqueous solution and CCl₄ solution using quantum mechanical methods. Gas-phase calculations were performed at the ab initio HF, MP2, and MP4 levels and solvent effects were investigated using a self-consistent reaction-field procedure adapted to the AM1 Hamiltonian. An almost planar arrangement was adopted by the-lactam ring in the three cases, whereas the alkoxycarbonyl side group was found to display a large conformational flexibility. The effects of the different solvents on the electrostatic properties of the three compounds were investigated by following the changes in both molecular electrostatic potentials and induced dipole moments. The resulting electrostatic parameters were used as static reactivity indices to predict the response of the systems to the attack of nucleophilic reagents. Theoretical results were compared with experimental data available on the structure and properties of-lactams. The validity of the method as a predicting tool was critically discussed.     

Corallocarpus epigaeus mediated synthesis of ZnO/CuO integrated ZrO2 nanoparticles for enhanced in-vitro antibacterial,antifungal and antidiabetic activities

Zirconia based nanocomposites have attracted much research attention in recent years due to their exceptional biomedicinal activities. Rhizome extracts of Corallocarpus epigaeus based ZrO₂/CuO–ZnO nanocomposite were green synthesized in a facile synthesis strategy. The nanocomposites were examined with XRD technique for their structural information and FT-IR technique for surface functional group analysis. Electron microscopic images aided to elucidate the CuO and ZnO nanoparticles decorated ZrO₂ nanostructures. UV–vis absorption spectroscopic studies of the nanocomposite revealed the characteristic UV absorption of ZrO₂ and enhanced visible region absorption for the incorporated nanoparticles. Antibacterial and antifungal studies indicated enhanced activity of nanocomposites over the pristine zirconia nanoparticles. ZrO₂/CuO–ZnO nanocomposite had exhibited about 75% of α-amylase inhibition activity, whereas pristine ZrO₂ nanoparticles had exhibited only 57% suggesting the worthwhile application in the antidiabetic activity of the nanocomposite.     

Radical cyclisations of methylenecyclopropyl azetidinones—synthesis of novel tricyclic β-lactams

Addition of lithium bis(methylenecyclopropyl)cuprates to acetoxy azetidinones gives methylenecyclopropyl azetidinones, which can be converted to various radical cyclisation precursors. Attempted 4-exo cyclisation of 3 led only to reduced product, while cyclisation of 5, using CuCl/bipy, gave a carbacephem, via a 5-exo cyclisation, but in low yield. Cyclisation of 6 and 7, however, gave novel tricyclic β-lactams, as the result of 7-endo cyclisation, in good yield, and a cyclisation of bromide 23 led to the tricyclic β-lactam 24, via a radical cascade sequence.     

Preparation and antibacterial activity of aromatic derivatives of β-aminopropionic and γ-aminobutyric acid

Ten aromatic derivatives of β-aminopropionic acid and γ-aminobutyric acid were prepared.Their compositions and structures were identified by elemental analysis,IR,and 1H NMR.They have been examined for their antibacterial action against Staphylococcua aurens and Escherichia coli.These compounds showed higher activity than the aromatic derivatives of ct-amino acid which were reported previously.The general conclusion to be drawn is that the distance between amino and carboxylic group in these molecules could affect their antibacterial activity.Furthermore,those compounds with p-methyl substituent in phenyl ring exhibit higher activity than the others,and all the compounds exhibit higher activity against Escherichia coli and against Staphylococcua aureus.