Structural characterization of ether lipids from the archaeon Sulfolobus islandicus by high‐resolution shotgun lipidomics

The molecular structures, biosynthetic pathways and physiological functions of membrane lipids produced by organisms in the domain Archaea are poorly characterized as compared with that of counterparts in Bacteria and Eukaryota. Here we report on the use of high‐resolution shotgun lipidomics to characterize, for the first time, the lipid complement of the archaeon Sulfolobus islandicus. To support the identification of lipids in S. islandicus, we first compiled a database of ether lipid species previously ascribed to Archaea. Next, we analyzed the lipid complement of S. islandicus by high‐resolution Fourier transform mass spectrometry using an ion trap‐orbitrap mass spectrometer. This analysis identified five clusters of molecular ions that matched ether lipids in the database with sub‐ppm mass accuracy. To structurally characterize and validate the identities of the potential lipid species, we performed structural analysis using multistage activation on the ion trap‐orbitrap instrument as well as tandem mass analysis using a quadrupole time‐of‐flight machine. Our analysis identified four ether lipid species previously reported in Archaea, and one ether lipid species that had not been described before. This uncharacterized lipid species features two head group structures composed of a trisaccharide residue carrying an uncommon sulfono group (?SO₃) and an inositol phosphate group. Both head groups are linked to a glycerol dialkyl glycerol tetraether core structure having isoprenoid chains with a total of 80 carbon atoms and 4 cyclopentane moieties. The shotgun lipidomics approach deployed here defines a novel workflow for exploratory lipid profiling of Archaea. Copyright © 2015 John Wiley & Sons, Ltd.     

Alkali-metal-ion catalysis and inhibition in the nucleophilic displacement reaction of y-substituted phenyl diphenylphosphinates and diphenylphosphinothioates with alkali-metal ethoxides: effect of changing the electrophilic center from P=O to P=S

A kinetic study of the nucleophilic substitution reaction of Y‐substituted phenyl diphenylphosphinothioates 2 a – g with alkali‐metal ethoxides (MOEt; M=Li, Na, K) in anhydrous ethanol at (25.0±0.1) °C is reported. Plots of pseudo‐first‐order rate constants (k_obsd) versus [MOEt], the alkali ethoxide concentration, show distinct upward (KOEt) and downward (LiOEt) curvatures, respectively, pointing to the importance of ion‐pairing phenomena and a differential reactivity of dissociated EtO^? and ion‐paired MOEt. Based on ion‐pairing treatment of the kinetic data, the k_obsd values were dissected into k and k_MOEt, the second‐order rate constants for the reaction with the dissociated EtO^? and ion‐paired MOEt, respectively. The reactivity of MOEt toward 2 b (Y=4‐NO₂) increases in the order LiOEt?NaOEt>KOEt>EtO^?. The current study based on Yukawa–Tsuno analysis has revealed that the reactions of 2 a – g (P?S) and Y‐substituted phenyl diphenylphosphinates 1 a – g (P?O) with MOEt proceed through the same concerted mechanism, which indicates that the contrasting selectivity patterns are not due to a difference in reaction mechanism. The P?O compounds 1 a – g are approximately 80‐fold more reactive than the P?S compounds 2 a – g toward the dissociated EtO^? (regardless of the electronic nature of substituent Y) but are up to 3.1×10³‐fold more reactive toward ion‐paired LiOEt. The origin of the contrasting selectivity patterns is further discussed on the basis of competing electrostatic effects and solvational requirements as a function of anionic electric field strength and cation size (Eisenman’s theory).     

Stereoselective Synthesis,Configurational Assignment and Biological Evaluations of the Lipid Mediator RvD2n-3 DPA

Herein we report the first total synthesis of RvD2_{n-3 DPA}, an endogenously formed mediator biosynthesized from the omega-3 fatty acid n-3 docosapentaenoic acid. The key steps are the Midland Alpine borane reduction, Sonogashira cross-coupling reactions, and a Z-selective alkyne reduction protocol, yielding RvD2_{n-3 DPA} methyl ester in 13 % yield over 12 steps (longest linear sequence). The physical property data (UV chromophore, chromatography and MS/MS fragmentation) of the synthetic lipid mediator matched those obtained from biologically produced material. Moreover, synthetic RvD2_{n-3 DPA} also carried the potent biological activities of enhancing macrophage uptake of Staphylococcus aureus and zymosan A bioparticles.     

Synthesis,Characterization, and Bioactivity of Novel Bicinnolines Having 1‐Piperazinyl Moieties

A number of novel bicinnolines containing piperazine moieties, 4a – o , were synthesized via polyphosphoric acid‐catalyzed intramolecular cyclization of the respective acyl amidrazone derivatives ( 3a – o ). On the other hand, the amidrazones ( 3a – o ) were prepared by reaction of N′,N″‐(biphenyl‐4,4′‐diyl)bis(2‐oxopropane hydrazonoyl chloride) ( 2 ) with the appropriate cyclic sec‐amines in the presence of trimethylamine in absolute ethanol. Structures of the newly synthesized compounds were confirmed by NMR and mass spectral data. The antitumor activity of compounds 4a – o was evaluated in vitro on human breast cancer MDA‐231 by a cell viability assay. Results revealed that compounds 4k , 4n , and 4o exhibit potential cytotoxic effects (>70%) on the cancer cells. Additionally, the antimicrobial activity of compounds 4a – o was evaluated against three clinical microbial strains: Escherichia coli (Gram‐negative bacteria), Staphylococcus aureus (Gram‐positive bacteria), and Candida albicans (fungi/yeast). Results revealed that compounds 4e and 4k exhibit good activity against all three strains included in the study and that compound 4d displays excellent activity against S. aureus strain with a minimum inhibitory concentration value of 0.187 mg/mL.     

CHARMM‐GUI Membrane Builder toward realistic biological membrane simulations

CHARMM‐GUI Membrane Builder, http://www.charmm‐gui.org/input/membrane , is a web‐based user interface designed to interactively build all‐atom protein/membrane or membrane‐only systems for molecular dynamics simulations through an automated optimized process. In this work, we describe the new features and major improvements in Membrane Builder that allow users to robustly build realistic biological membrane systems, including (1) addition of new lipid types, such as phosphoinositides, cardiolipin (CL), sphingolipids, bacterial lipids, and ergosterol, yielding more than 180 lipid types, (2) enhanced building procedure for lipid packing around protein, (3) reliable algorithm to detect lipid tail penetration to ring structures and protein surface, (4) distance‐based algorithm for faster initial ion displacement, (5) CHARMM inputs for P₂₁ image transformation, and (6) NAMD equilibration and production inputs. The robustness of these new features is illustrated by building and simulating a membrane model of the polar and septal regions of E. coli membrane, which contains five lipid types: CL lipids with two types of acyl chains and phosphatidylethanolamine lipids with three types of acyl chains. It is our hope that CHARMM‐GUI Membrane Builder becomes a useful tool for simulation studies to better understand the structure and dynamics of proteins and lipids in realistic biological membrane environments. © 2014 Wiley Periodicals, Inc.     

Warum pentose-und nicht hexose-nucleinsäuren? Teil III. Oligo(2′,3′-dideoxy-β-D-glucopyranosyl) nucleotide (‘homo-DNS’): Paarungesigenschaften

Why Pentose-And Not Hexose-Nucleic Acids? Part III. Oligo(2′,3′-dideoxy-β-D -glucopyranosyl)nucleotides. (‘Homo-DNA’): Base-Pairing Properties

1 Summary in collaboration with Prof. Dr. C. E. Wintner, Haverford College, Haverford, PA 19041-1392.

The paper presents results of a comprehensive investigation on the pairing properties of homo-DNA oligonucleotides, the preparation of which has been described in Part II of this series [2]. The investigation was carried out by using established methods described in the literature for the characterization of oligonucleotides in the natural series, such as determination of melting temperatures of oligonucleotide duplexes by temperature-dependent of melting temperatures, determination of pairing stoichiometry by ratio-dependent UV spectroscopy of binary mixtures of pairing partners, temperature-dependent CD spectroscopy, gel electrophoresis under non-denaturing conditions, and – in selected cases – ¹H – and³¹P-NMR spectroscopy. The systematic comparison of the paring properties of homo-DNA oligonucleotides with corresponding DNA nucleotides (up to dodecamers) indicates that homo-DNA is a highly efficient, autonomous, artificial pairing system with a pairing behavior that is in part similar to, but also, in part, strikingly different from, the pairing behavior of DNA. The pairing properties established so far are listed below in a manner that reflects the sequence of subtitles in Chapt.2 of the text; they were determined under the conditions: H²O, 0.15M NaCl, 0.01M Tris-HCl buffer, pH 7, oligonucleotide concentrations in the μM range, 1:1 ratio of single strands in the case of non-selfcompementary sequences.     

Effect of Na+ and Ca2+ Ions on a Lipid Langmuir Monolayer: An Atomistic Description by Molecular Dynamics Simulations

Studying the effect of alkali and alkaline‐earth metal cations on Langmuir monolayers is relevant from biophysical and nanotechnological points of view. In this work, the effect of Na⁺ and Ca²⁺ on a model of an anionic Langmuir lipid monolayer of dimyristoylphosphatidate (DMPA^?) is studied by molecular dynamics simulations. The influence of the type of cation on lipid structure, lipid–lipid interactions, and lipid ordering is analyzed in terms of electrostatic interactions. It is found that for a lipid monolayer in its solid phase, the effect of the cations on the properties of the lipid monolayer can be neglected. The influence of the cations is enhanced for the lipid monolayer in its gas phase, where sodium ions show a high degree of dehydration compared with calcium ions. This loss of hydration shell is partly compensated by the formation of lipid–ion–lipid bridges. This difference is ascribed to the higher charge‐to‐radius ratio q/r for Ca²⁺, which makes ion dehydration less favorable compared to Na⁺. Owing to the different dehydration behavior of sodium and calcium ions, diminished lipid–lipid coordination, lipid–ion coordination, and lipid ordering are observed for Ca²⁺ compared to Na⁺. Furthermore, for both gas and solid phases of the lipid Langmuir monolayers, lipid conformation and ion dehydration across the lipid/water interface are studied.     

Synthesis and Characterization of Neutral Cyclometalated Platinum(II) Complexes and their Antibacterial and Cytotoxic Evaluations

A series of neutral cyclometalated platinum(II) complexes bearing 2,6-bis(2-naphthyl)pyridine as a C^N^C tridentate chelating ligand with monodentate pyridyl ligands with different substituents 1 – 3 have been synthesized via double cyclometalation and ligand displacement reaction. The structural, photophysical, electrochemical and aggregation induced emission (AIE) properties of these neutral platinum(II) complexes were systematically studied. Complexes 1 – 3 exhibited AIE effects with different emission intensities and colors, in which 1 showed the highest quantum efficiency of 8.6 % under aggregated state, and the aggregates were assembled to ordered spheres. Among the Pt(II) complexes, 1 showed a bactericidal activity against both Staphylococcus aureus (S. aureus) (MIC and MBC=3.13 μg/mL) and methicillin-resistant S. aureus (MRSA) (MIC and MBC=6.25 μg/mL). Complex 1 did not possess noticeable cytotoxicity to human skin HaCaT keratinocytes. The non-cytotoxic complex 1 would have a good potential to be used for the antibacterial therapy to combat with S. aureus and MRSA-infected skin diseases.     

Spectral Characterization and Antimicrobial Activity of Some Schiff Bases Derived from 4‐Methyl‐2‐aminophenol

A series of N‐(5‐methyl‐2‐hydroxyphenyl)‐(2/3/4/5‐substituted)‐benzaldimines ( I – XIII ) were synthesized using appropriate synthetic route. Their structures were characterized by FT‐IR, UV‐Visible, ESI‐MS, ¹H‐ and ¹³C‐NMR spectroscopic techniques and analytical methods. The crystal structure of N‐(5‐methyl‐2‐hydroxyphenyl)‐3,4‐dimethoxybenzaldimine ( XIII ) was determined by X‐ray diffraction at room temperature. Relationship between the melting points and the structures of the compounds were examined. Antibacterial activities of the compounds were evaluated against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Proteus mirabilis. Antifungal activities were reported for Candida albicans. Some of the Schiff bases showed considerable antimicrobial activity against S. aureus and C. albicans.     

Spectral Characterization and Antimicrobial Activity of Some Schiff Bases Derived from 4‐Chloro‐2‐aminophenol and Various Salicylaldehyde Derivatives

A series of N‐(5‐chloro‐2‐hydroxyphenyl)‐(3/4/5‐substituted)‐salicylaldimines ( I – XI ) were synthesized using appropriate synthetic route. Their structures were characterized by FT‐IR, UV‐Visible, ESI‐MS, ¹H and ¹³C NMR spectroscopic techniques and analytical methods. The crystal structure of N‐(5‐chloro‐2‐hydroxyphenyl)‐5‐bromosalicylaldimine ( V ) was determined by X‐ray diffraction at room temperature. Relationship between the melting points and the structures of the compounds was examined. Antimicrobial activity of the compounds was evaluated against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis. Antifungal activities were reported for Candida albicans. Schiff bases showed considerable antimicrobial activity against S. aureus, S. epidermidis and C. albicans. N‐(5‐Chloro‐2‐hydroxyphenyl)‐3‐hydroxy‐salicylaldimine ( II ) has the broadest and highest antimicrobial activity according to the others.     

Complementary precursor ion and neutral loss scan mode tandem mass spectrometry for the analysis of glycerophosphatidylethanolamine lipids from whole rat retina

A “shotgun” tandem mass spectrometry (MS) approach involving the use of multiple lipid-class-specific precursor ion and neutral loss scan mode experiments has been employed to identify and characterize the glycerophosphatidylethanolamine (GPEtn) lipids that were present within a crude lipid extract of a normal rat retina, obtained with minimal sample handling prior to analysis. Characterization of these lipids was performed by complementary analysis of their protonated and deprotonated precursor ions, as well as their various ionic adducts (e.g., Na⁺, Cl^-), using a triple-quadrupole mass spectrometer. Notably, the application of novel precursor ion and neutral loss scans of m/z 164 and m/z 43, respectively, for the specific identification of sodiated GPEtn precursor ions following the addition of 500 μM NaCl to the crude lipid extracts was demonstrated. The use of these novel MS/MS scans in parallel provided simplified MS/MS spectra and enhanced the detection of 1-alkenyl, 2-acyl (plasmenyl) GPEtn lipids relative to the positive ion mode neutral loss m/z 141 commonly used for GPEtn analysis. Furthermore, the novel use of a “low energy” neutral loss scan mode experiment to monitor for the exclusive loss of 36m/z (HCl) from [M+Cl]^- GPEtn adducts was demonstrated to provide a more than 25-fold enhancement for the detection of GPEtn lipids in negative ion mode analysis. Subsequent “high-energy” pseudo MS³ product ion scans on the precursor ions identified from this experiment were then employed to rapidly characterize the fatty acyl chain substituents of the GPEtn lipids. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.

Interaction between the antibacterial compound,oleuropein, and model membranes

Oleuropein, a secoiridoid glycoside extracted from the olive tree, Olea europaea L., has been described as showing antibacterial properties. However, the exact mechanism of these antimicrobial properties is not yet well understood. In the present study, we have studied the interaction of oleuropein with phosphatidylglycerol (PG) as a model membrane for Staphylococcus aureus (S. aureus) (Gram-positive bacteria) and phosphatidylethanolamine and Escherichia coli (E. coli) lipid extract as a model membrane for E. coli (Gram-negative bacteria). The study has been carried out using monolayers as model membranes and using kinetics at constant area and compression isotherms with Brewster angle microscopy (BAM) observations. The results show that oleuropein interacts in higher extent with PG monolayers, which is related with its stronger antibacterial effect against Gram-positive bacteria. The effects on the membrane are probably produced at the cell surface because oleuropein did not form stable mixed monolayers with the lipids assayed at the air/water interface.     

Fast and Reliable Automated Synthesis of RNA and Partially 2′-O- Protected Precursors (`Caged RNA') Based on Two Novel,Orthogonal 2′-O-Protecting Groups,Preliminary Communication

Two sets of RNA phosphoramidites, carrying the (fluoride-labile) 2′-O-[(triisopropylsilyl)oxy]methyl (=tom) group and the (photolabile) [(R)-1-(2-nitrophenyl)ethoxy]methyl (=(R)-npeom) group, were prepared (see 1 – 4 and 5 – 8 , resp.). The two protecting groups were completely orthogonal to each other. Three ribozyme-substrate constructs, protected each by a (R)-npeom group, were synthesized; on photolysis, efficient cleavage of this remaining protecting group occurred (Scheme 3). It could be demonstrated that the presence of one (R)-npeom group within a RNA strand has only a minor influence on the pairing properties of corresponding duplexes.     

Spectroscopic characterization of bionanoparticles originating from newly developed self-forming synthetic PEGylated lipids (QuSomes)

In this work, we have aimed to merge the advantages of nanotechnology and biophotonics in conjunction with vibrational spectroscopic techniques in order to understand the various aspects of new kinds of synthetic bionanoparticles originating from self-forming synthetic biopolymers known as polyethylene glycol (PEG)ylated lipids. In particular, two complementary molecular spectroscopic techniques based on thin-layered Fourier transform infrared and confocal laser tweezers. Raman spectroscopy has been employed for the investigations of newly developed artificial PEGylated lipids trademarked as QuSomes. These novel types of synthetic lipids are composed of 1,2-dimyristoyl-rac-glycerol-3-dodecaethylene glycol (GDM-12), 1,2-dioleoyl-rac-glycerol-3-dodecaethylene glycol (GDO-12), and 1,2-distearoyl-rac-glycerol-3-triicosaethylene glycol (GDS-23). The lipid labeled GDM-12 has saturated 14 acyl chains whereas GDO-12 is characterized by monounsaturated 18 acyl chains, and GDS-23 is composed of saturated 18 acyl chains in their hydrophobic chain. Similarly, GDM-12 and GDO-12 contain 12 units, and GDS-23 contains 23 units of hydrophilic PEG head groups. In contrast to conventional phospholipids, this novel kind of lipid can form liposomes spontaneously upon hydration, without the input of external activation energy. In addition, fluorescence correlation spectroscopy has been utilized to measure the size distribution of such nanoparticles in suspension as well as scanning electron microscopy has been applied for the imaging purposes. Although such PEGylated lipids show a common spectral pattern, important differences in the spectra have been observed, enabling us to distinguish these different lipids on the basis of characteristic features calculated from the spectroscopic band component analysis. Finally, in this study, detailed spectroscopic results due to the vibrational band assignments and band component analysis corresponding to various functional groups for individual nanoparticles have been analyzed and discussed.     

A Novel Synthesis of 4‐Pyridazineacetic Acids via Ring Expansion of N‐Cyanomethylated 3‐Pyrazoline‐4‐acetic Acids

A novel synthetic route to 4‐pyridazineacetic acids 10 – 12 has been achieved by the ring‐expansion reaction of N‐cyanomethylated 3‐pyrazoline‐4‐acetic acids 7 – 9 . 1H‐Pyrazole‐4‐acetic acids 1 – 3 were reacted with iodoacetonitrile in the presence of triethylamine in refluxing acetonitrile to give the corresponding C‐cyanomethylated 1H‐pyrazole‐4‐acetic acids 4 – 6 as major products together with N‐cyanomethylated 3‐pyrazoline‐4‐acetic acids 7 and 8 as minor products. On the other hand, reactions of 1 and 3 with chloroacetonitrile in the presence of triethylamine in refluxing chloroform afforded the corresponding N‐cyanomethylated 3‐pyrazoline‐4‐acetic acids 7 and 9 as major products. Thermal treatment of 7 – 9 with sodium hydride in N,N‐dimethylformamide caused ring expansion to yield the corresponding 4‐pyridazineacetic acids 10 – 12 .     

Ion Pairing and Salt Structure in Organic Salts through Diffusion,Overhauser, DFT and X‐ray Methods

Pulsed gradient spin‐echo (PGSE) diffusion characteristics for a) the new [brucinium][X] salts 6 a – f [ a : X=BF₄^?; b : X=PF₆^?; c : X=MeSO₃^?, d : X=CF₃SO₃^?; e : X=BArF^?; f : X=PtCl₃(C₂H₄)^?], b) 4‐tert‐butyl‐N‐benzyl analogue, 7 and c) the aryl carbocations (p‐R‐C₆H₄)₂CH 9 a (R=CH₃O) and 9 b (R=(CH₃)₂N), (p‐CH₃O‐C₆H₄)_xCPh_3?x⁺ 10 a – c (x=1–3, respectively) and (p‐R‐C₆H₄)₃C⁺ 11 (R=(CH₃)₂N) and 12 (R=H) all in several different solvents, are reported. The solvent dependence suggests strong ion pairing in CDCl₃, intermediate ion pairing in CD₂Cl₂ and little ion pairing in [D₆]acetone. ¹H, ¹⁹F HOESY NMR spectra (HOESY: heteronuclear Overhauser effect spectroscopy) for 6 and 7 reveal a specific approach of the anion with respect to the brucinium cation plus subtle changes, which are related to the anion itself. Further, for carbocations 9 – 12 , (all as BF₄^? salts) based on the NOE results, one finds marked changes in the relative positions of the BF₄^? anion. In these aryl cationic species the anion can be located either a) very close to the carbonium ion carbon b) in an intermediate position or c) proximate to the N or O atom of the p‐substituent and remote from the formally positive C atom. This represents the first example of such a positional dependence of an anion on the structure of the carbocation. DFT calculations support the experimental HOESY results. The solid‐state structures for 6 c and the novel Zeise's salt derivative, [brucinium][PtCl₃(C₂H₄)], 6 f , are reported. Analysis of ¹⁹⁵Pt NMR and other NMR measurements suggest that the η²‐C₂H₄ bonding to the platinum centre in 6 f is very similar to that found in K[PtCl₃(C₂H₄)]. Field dependent T₁ measurements on [brucinium][PtCl₃(C₂H₄)] and K[PtCl₃(C₂H₄)], are reported and suggested to be useful in recognizing aggregation effects.     

Ultrasound‐assisted Synthesis of Novel Pyrazole and Pyrimidine Derivatives as Antimicrobial Agents

Herein, we report a convenient and facile methodology for the synthesis of new series of pyrazole and pyrimidine derivatives 2a – f and 3a – f under ultrasound irradiation. Pyrazole and pyrimidine derivatives have been synthesized in better yields and shorter reaction times compared with the conventional method. The chemical structures of all the synthesized compounds were elucidated by their IR, ¹H NMR, ¹³C NMR, MS, and elemental analysis. Further, the target compounds were screened for their antimicrobial activity against four bacteria (Staphylococcus aureus, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa) and two fungi (Candida albicans, Aspergillus niger). In particular, compounds 2a , 2d , 2e , 3a , 3e , and 3f exhibited potent antimicrobial activity.     

Replacement of Canonical DNA Nucleobases by Benzotriazole and 1,2,3‐Triazolo[4,5‐d]pyrimidine: Synthesis,Fluorescence, and Ambiguous Base Pairing

The syntheses and the fluorescence properties of 7H‐3,6‐dihydro‐1,2,3‐triazolo[4,5‐d]pyrimidin‐7‐one 2′‐deoxy‐β‐D ‐ribonucleosides (=2′‐deoxy‐8‐azainosine) 3 (N³), 15 (N²), and 16 (N¹) as well as of 1,2,3‐benzotriazole 2′‐O‐methyl‐β‐ or ‐α‐D ‐ribofuranosides 6 (N¹) and 24 (N¹) are described. Also the fluorescence properties of 1,2,3‐benzotriazole 2′‐deoxy‐β‐D ‐ribofuranosides 4 (N¹) and 5 (N²) are evaluated. From the nucleosides 3 – 6 , the phosphoramidites 19, 26a, 26b , and 28 are prepared and employed in solid‐phase oligonucleotide synthesis. In 12‐mer DNA duplexes, compound 3 shows similar ambiguous base‐pairing properties as 2′‐deoxyinosine ( 1 ), while the nucleosides 4 – 6 show strong pairing with each other and discriminate very little the four canonical DNA constituents.     

Synthesis of Some N-Alkoxycarbonyl-N″-benzoyl-benzamidrazones（p-toluamidrazones） and 1,3,5-Trisubstituted 1,2,4-Triazole Derivatives from N-Benzoylimidates and their Antimicrobial and Anticancer Screening Studies

Some new N-alkoxycarbonyl-N″-benzoyl-benzamidrazones （p-toluamidrazones） 3a-3d, and 1,3,5-trisubstituted 1,2,4-triazole 4a-4h derivatives by starting from N-benzoylbenzimidates or N-benzoyl-p-toluimidates. The structures of compounds 3 and 4 were established on the basis of elemental analyses, IR, ^1H NMR, ^13C NMR and UV data. Antimicrobial experiments of the compounds performed by using agar-well diffusion and broth microdilution methods revealed that only compounds 3a-3d, 4a and 4b showed inhibitory effect only on Candida albicans ATCC 60193. However, compound 4b had also specific antibacterial activity against Staphylococcus aureus ATCC 25923. The other compounds showed neither antifungal nor antibacterial activities. Compounds 3a, 4a and 4b have been screened on three human tumor cell lines, breast cancer （MCF7）, non small cell lung cancer （NCI-H460）, and CNS cancer （SF-268） at the National Cancer Institute （NCI）, USA, which were found to exhibit low antiproliferative activity.