Herbicidal Activity of Phosphonic,Phosphinic and Phosphinous Acid Analogues of Aromatic Amino Acids

Abstract

Over 40 phosphonic, phosphinic and phosphinous acid analogues of phenylglycine and phenylalanine were synthesized and screened for their herbicidal activity on Lepidium sativum (crest) and Cucumis sativus (cucumber). The most active appeared to be 2-amino-1-hydroxy-3-phenylpropylphosphonic acid which was equipotent with popular herbicide glyphosate. Also aminobenzylphosphonic acids, analogues of phenylglycine, exhibited notable herbicidal activity and thus represent a group of the most active herbicides found among simple aminophosphonic acids. Other compounds showed moderate herbicidal activity. Preliminary results indicate that analogues of aromatic amino acids display their activity as effectors of biosynthesis of aromatic amino acids.     

Antimicrobial activity-guided identification of compounds from the deciduous leaves of Malus doumeri by HPLC-ESI-QTOF-MS/MS

This paper intends to identify the antimicrobial activity compounds from the deciduous leaves of Malus doumeri (Dong Li Tea) by HPLC-ESI-QTOF-MS/MS. The ethanol extracts of Malus doumeri were partitioned into petroleum ether, dichloromethane, ethyl acetate, n-butanol and water fraction, respectively. The antimicrobial screening experiments showed that ethyl acetate fraction has a certain antibacterial activity by inhibition zone method in vitro. And then we used the HPLC-ESI-QTOF-MS/MS method to verify the identities of bioactive compounds. Finally, 41 compounds were determined and 11 of which were firstly reported in this plant. Notably, compounds (32, 34, 38) are new dihydrochalcones, and three chlorogenic acid analogues (10, 13, 17) may be potential antimicrobial active ingredient. Which is of great significance to the isolation of novel compounds and the discovery of new natural preservative candidates from the deciduous leaves of Malus doumeri.     

Conjugates with an Antimicrobial Effect Based on New Derivatives of Mercaptobenzoxazole Esterified onto Poly(maleic anhydride‐alt‐vinyl acetate)

New compounds with biological activity based on hydroxy‐amino derivatives of benzoxazolyl‐2‐mercaptoformic acid, benzoxazolyl‐2‐mercaptoacetic acid, and chloracetyl‐2‐mercaptobenzoxazole have been synthesized. The chemical bonding of these compounds to poly(maleic anhydride‐alt‐vinyl acetate), through esterification, leads in obtaining conjugates of polymer biologically active compound type, tests indicating a sustained release of the active chemical, with time (between 5 and 6 h). Reaction products were characterized through elemental and spectral analysis (FTIR and ¹H NMR). Toxicology and antimicrobial activity tests recommend compounds with small molecule, as well as their conjugates as therapeutical candidates (antimicrobial inhibitors) for pharmacological application.     

Design,Synthesis, In Vitro Antimicrobial,Antioxidant Evaluation,and Molecular Docking Study of Novel Benzimidazole and Benzoxazole Derivatives

A series of novel 2‐substituted benzimidazole and benzoxazole derivatives as a potential antimicrobial and antioxidant agent were synthesized via coupling of N‐methyl‐o‐phenylenediamine or 2‐amino‐phenol with aromatic aldehyde and acid in the presence of polyphosphoric acid as an efficient catalyst as well as solvent by conventional method in short reaction times with excellent yield. The newly synthesized benzimidazole and benzoxazole derivatives were evaluated for antimicrobial and antioxidant activity and exhibited excellent to good activities compared to the standard drugs. Furthermore, the theoretical predictions based on molecular docking against microbial DNA gyrase could provide an insight into the plausible mechanism of action and establish a link between the observed antimicrobial activity and the binding affinity shedding light on specific thermodynamic (bonded and nonbonded) interactions governing the activity. Furthermore, the synthesized compounds were analyzed for absorption, distribution, metabolism, and excretion properties and exhibited potential properties to build up as good oral drug candidates.     

Selective Photoinactivation of Methicillin-Resistant Staphylococcus aureus by Highly Positively Charged RuII Complexes

Ruthenium(II) polypyridyl complexes featuring peripheral quaternary ammonium structures were found to be able to selectively inactivate Gram-positive Staphylococcus aureus (S. aureus), including methicillin-resistant S. aureus (MRSA) upon visible light irradiation, but have low phototoxicity toward 293T cells, L02 cells and lack hemolysis toward rabbit red blood cells (RBC), exhibiting promising potential as a novel type of antimicrobial photodynamic therapy (aPDT) agents.     

Synthesis,Photophysical Properties,and Antimicrobial Activity of Novel Styryl Colorants Derived from 7‐Methoxy‐1,4‐diphenethyl‐1,2,3,4‐tetrahydroquinoxaline‐6‐carbaldehyde

The novel 1,4‐diphenethyl‐1,2,3,4‐tetrahydro‐7‐methoxyquinoxalin‐6‐carbaldehyde was synthesized by reductive alkylation of 6‐methoxy quinoxaline with phenyl acetic acid and was further subjected to Knoevenagel condensation with various active methylene compounds to synthesize novel styryl colorants. Photophysical properties of styryl colorants were studied using UV–visible and fluorescence spectroscopy. These colorants displayed orange to violet hue and showed fluorescence emission maxima in the region of 560–640 nm, and displayed a large Stokes shift (85–104 nm). Compounds were subjected to thermogravimetric analysis which showed excellent stability up to 310°C. These styryl compounds were evaluated for their antimicrobial study as antifungal against Candida albicans C. albicans and Aspergillus niger and antibacterial against Escherichia coli and Staphylococcus aureus. The results revealed good antimicrobial activity against tested organisms. The synthesized chromophores were characterized using elemental analysis, FTIR, ¹³C‐NMR and ¹H‐NMR spectroscopy and mass spectrometry.     

Synthesis of new antimicrobial 4-aminosubstituted 3-nitrocoumarins

A series of new coumarin derivatives has been synthesized by condensation of 4-chloro-3-nitrocoumarin and the appropriate arylamine and sulfonamide in ethyl acetate in the presence of triethylamine. The synthesized compounds were screened for their in vitro antimicrobial activity against thirteen strains of bacteria and three fungal/yeast strains using disk diffusion assays. They were shown to possess a wide range of activities from almost completely inactive compounds to medium active ones. (4-[(5-Chloropyridin-2-yl)amino]-3-nitro-2H-chromen-2-one) showed similar activity against Klebsiella pneumoniae as tetracycline.     

Spectroscopic,thermal and antimicrobial properties of the copper(II) complex of Schiff base derived from 2‐(salicylidene) aminopyridine

Schiff bases and their complex combinations with metallic ions represent a class of compounds with antimicrobial activity. A ligand was prepared by condensation of the salicylaldehyde with 2‐aminopyridine obtaining 2‐(salicylidene) aminopyridine (SB) with a high capacity for complexing Cu(II) ions. The new compound has been characterized by physical constants (melting point, solubility, stability) and the chemical structure was confirmed by elemental, spectral (IR, UV–visible, ¹H NMR and ¹³C‐NMR) and thermal analyses. The elemental analysis gives a coordination ratio of 1:2 metal:Schiff base. Lethal dose 50 (DL₅₀) values of new Schiff base and their complex with metallic ions were established. The antimicrobial activity of this complex was tested in comparison with the activity of the corresponding Schiff base on strains of Staphylococcus aureus, Bacillus cereus, Bacillus subtilis, Escherichia coli, Candida albicans, and Klebsiella. These were compared with the activity of the reference drugs (chloramphenicol, tetracycline, ofloxacin and nystatin) on the above‐mentioned strains. It has been established that all compounds tested were very active against both Gram‐positive and Gram‐negative bacteria. Copyright © 2012 John Wiley & Sons, Ltd.     

A Versatile Boc Solid Phase Synthesis of Daptomycin and Analogues Using Site Specific,On-Resin Ozonolysis to Install the Kynurenine Residue

A de novo solid-phase synthesis of the cyclic lipodepsipeptide daptomycin via Boc chemistry was achieved. The challenging ester bond formation between the nonproteinogenic amino acid kynurenine was achieved by esterification of a threonine residue with a protected tryptophan. Subsequent late-stage on-resin ozonolysis, inspired by the biomimetic pathway, afforded the kynurenine residue directly. Synthetic daptomycin possessed potent antimicrobial activity (MIC₁₀₀=1.0 μg mL⁻¹) against S. aureus, while five other daptomycin analogues containing (2R,3R)-3-methylglutamic acid, (2S,4S)-4-methylglutamic acid or canonical glutamic acid at position twelve prepared using this new methodology were all inactive, clearly establishing that the (2S,3R)-3-methylglutamic acid plays a key role in the antimicrobial activity of daptomycin.     

A Facial Synthesis and Anticancer Activity of (Z)‐2‐((5‐(4‐nitrobenzylidene)‐4‐oxo‐4,5‐dihydrothiazol‐2‐yl)amino)‐substituted Acid

In order to explore the anticancer and antimicrobial activity associated with the thiazole framework, we synthesized the new series (Z )‐2‐((5‐(4‐nitrobenzylidene)‐4‐oxo‐4,5‐dihydrothiazol‐2‐yl)amino)‐substituted acid derivatives 6a – l . All the synthesized compounds were evaluated for anticancer and antimicrobial activity in vitro. Among these, the compounds 6a , 6b, 6c , 6e , 6f , 6g , 6h , 6i , 6j , and 6k showed highest antibacterial and antifungal activity. The compound 6a exhibited significant antibacterial activity against Bacillus subtilis , whereas compound 6j displays significant antifungal activity against fungal strains, that is, A. oryzae . The in vitro anticancer studies revealed that 6e , 6g , 6h , 6k , and 6l are the most active compounds against MCF‐7 and BT‐474 human breast cancer cell lines, which can be regarded as the promising drug candidate for development of anticancer drugs.     

Design,synthesis, and antimicrobial evaluation of some nifuroxazide analogs against nosocomial infection

A series of 10 p-substitutedbenzoylmethylene hydrazide derivatives 4a-j were synthesized by protecting carboxylic group of 4-hydroxybenzoic acid using methanol and sulfuric acid than reacting it with hydrazide to form 4-hydroxybenzohydrazide followed by reacting with a variety of aldehydes and evaluated for their activity against nosocomial infection. All the synthesized compounds were characterized by Fourier-transform infrared (FT-IR), ¹H nuclear magnetic resonance (NMR), and mass spectral data. The in vitro antimicrobial potential of synthesized compounds was estimated against prominent strains of nosocomial pathogens (Staphylococcus aureus, Escherichia coli, and Aspergillus niger). The antimicrobial evaluation revealed compounds 4b , 4c , 4d , 4e , 4f , and 4j to be the most active compounds of the series with IC₅₀ value for antibacterial in the range 0.39 to 0.75 μM/mL. Furthermore, the in vitro cytotoxic potential of the compounds was appraised by hemolytic assay. The results showed that some of the synthesized compounds exhibited marked activity.     

Synthesis and antimicrobial activities of 4-aryl-3,4-dihydrocoumarins and 4-arylcoumarins

A new series of 4-aryl-3,4-dihydrocoumarins and 4-arylcoumarins were synthesized by the reaction of substituted cinnamic acids and 3-arylpropiolic acid with the corresponding phenols. These compounds were evaluated for antibacterial activity in vitro. The synthesized compounds displayed different degrees of antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Bacillus dysenteriae, and Candida albicans (a fungus). Compounds with catechol moieties and 7,8-substituted dihydroxyls in the A ring were the most active antimicrobial agents.     

Design,Synthesis and Antimicrobial Evaluation of Novel Tricyclic Benzoxazine Fluoroquinolones under Conventional and Microwave Methods

In view of obtaining some potential antimicrobial compounds, we have described synthesis of novel fluoroquinolones bearing 2‐(piperidin‐4‐yl)‐1H‐benzo[d]imidazole and evaluated for their antimicrobial activity. Alternatively, synthesis of these products was also demonstrated using microwave irradiation technique. The antimicrobial activity of newly synthesized compounds was evaluated against number of microorganisms and the activity is compared with highly active levofloxacin.     

Synthesis and in vitro Antimicrobial Activity of Nalidixic Acid Hydrazones

A series of nalidixic acid‐based hydrazones have been synthesized and evaluated for their in vitro antimicrobial activity using the broth microdilution method against a panel of reference strains of microorganisms, including Gram‐positive bacteria, Gram‐negative bacteria, and fungi belonging to yeasts Candida spp. and molds Aspergillus spp., Penicillium spp., and Rhizopus spp. Nalidixic acid derivatives were obtained by condensation reaction of nalidixic acid hydrazide with substituted (hetero)aromatic aldehydes. All compounds have been characterized by ¹H NMR and ¹³C NMR spectra. The antimicrobial activity indicated that compound with indole substituent could be a promising lead for future development of active antifungal agents.     

Synthesis and Antimicrobial Activity of 2-Methyl-5-nitroaniline Derivatives:A Structure-Activity Relationship Study

A series of 2‐methyl‐5‐nitroaniline derivatives, 5a – 5k and 6a – 6f , were synthesized in order to determine their in vitro antimicrobial activity. The chemical structures of the synthesized compounds were confirmed by elemental analyses, UV‐visible, FT‐IR, ¹H NMR and ¹³C NMR spectral studies. The structure‐activity relationships of the synthesized compounds were also discussed. Among the synthesized compounds, 5f , 5d , 6b and 6e showed good antimicrobial activity compared to standard drugs.     

Indoline-3-carboxylic acid derived organocatalysts for the anti-Mannich reaction

Mannich type reactions of a preformed aldimine with various carbonyl compounds were investigated with a series of functionalised indoline derivatives as catalysts: indoline‐3‐carboxylic acid, the diphenylcarbinol analogue and O‐protected silyl ether analogues. All compounds were readily prepared in enantiopure form by using an enzymatic kinetic resolution as a key step (E?100). The alcohol and ether catalysts failed to induce complete chirality transfer but did afford the Mannich bases in good yields and high diastereomeric ratios, whereas the acid catalyst gave the products in a highly diastereo‐ and enantioselective manner. The absolute configuration of the products was determined by a syn–anti isomerisation protocol, initiated by the sterically demanding base 1,8‐diazabicyclo[5.4.0]undec‐7‐ene.     

Antimicrobial evaluation of selected naturally occurring oxyprenylated secondary metabolites

This study tested the antimicrobial activity of eight selected naturally occurring oxyprenylated secondary metabolites against Staphylococcus aureus ATCC 29213, S. epidermidis ATCC 35984, Escherichia coli ATCC 8739, Pseudomonas aeruginosa ATCC 9027 and Candida albicans ATCC 10231. Results showed a moderate antimicrobial activity. The most active compounds were 3-(4-geranyloxyphenyl)-1-ethanol (4) and 3-(4-isopentenyloxyphenyl)-1-propanol (5) that were tested on mature and in-formation biofilms of all micro-organisms, moreover the cytotoxic activity was evaluated. Except for S. epidermidis, both compounds reduced significantly (p < 0.05) the microbial biofilm formation at 1/2 MIC and 1/4 MIC, in particular, compounds 4 and 5 at each concentration, inhibited E. coli biofilm formation to a greater extent, the biofilm formation was never more than 44% in respect to the control, moreover both compounds showed a low cytotoxic effect. Oxyprenylated derivatives may be of great interest for the development of novel antimicrobial therapeutic strategies and the synthesis of semi-synthetic analogues with anti-biofilm efficacy.     

Novel Synthesis of 2-(2-(3-Hydroxy-5-oxo-4-phenylthiophen-2(5H)-ylidene)-2-phenylacetamido)propanoic Acid Analogues and Their Anti-Inflammatory Properties

This article describes the reaction of 3,6-diphenyl-thieno[3,2-b]furan-2,5-dione 1 with different amino acids 2a–j in glacial acetic acid which afforded the 2-(2-(3-hydroxy-5-oxo-4-phenylthiophen-2(5H)-ylidene)-2-phenylacetamido)propanoic acid analogues 3a–j and also describes the reaction of 3,6-diphenyl-thieno[3,2-b]thiophene-2,5-dione 4 with different amino acids 5a–e in acidic medium to give 2-(2-(3-mercapto-5-oxo-4-phenylthiophen-2(5H)-ylidene)-2-phenylacetamido)propanoic acid analogues 6a–e. All the compounds have been screened for their anti-inflammatory activity against the carrageenan induced rat paw edema in albino rats. In the primary screening, some of the compounds exhibited appreciable activity.

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.     

Evaluation of bactericidal and fungicidal activity of ferrocenyl or phenyl derivatives in the diphenyl butene series

Some ferrocene compounds, such as tamoxifen derivatives hydroxyferrocifen 1 and ferrociphenol 2, show strong antiproliferative activity on hormone-dependent and hormone-independent breast cancer cells. In order to evaluate their antimicrobial activity, they were tested, together with their purely organic analogs, on the bacteria Pseudomonas aeruginosa and Staphylococcus aureus and the fungus Candida albicans. It has been found that the compounds bearing alkylamino chains are active, and in these cases the antimicrobial activity increases for compounds bearing two amino chains. These dialkyamino compounds are equally as active as doxycycline on P. aeruginosa and S. aureus but superior to it on C. albicans. The results show that there are no general correlation between the antitumoral activity and the bactericidal and fungicidal activities of these compounds. The ferrocene derivatives and their organic analogs have similar activity on bacteria and fungus. This bactericidal and fungicidal behaviour is a novel area of activity for these entities.     

PHYTOCHROME-MEDIATED RAPID CHANGES IN THE LEVEL OF PHOSPHOINOSITIDES IN ETIOLATED LEAVES OF Zea mays

The role of the active form of phytochrome in Zea mays on the polyphosphoinositide cycle was studied. As little as 15 s of red irradiation of etiolated leaves immediately increased the level of phosphatidylinositol bisphosphate (PIP₂) 3–6-fold compared to unirradiated leaves. The elevated level of PIP₂ decreased with longer red irradiations up to 5 min, but remained higher than in unirradiated leaves. The level of PIP₂ decreased if red irradiation was followed by far-red irradiation. Far-red alone had no effect. Levels of phosphatidylinositol phosphate (PIP) and phosphatidylinositol did not change significantly. Since red irradiation significantly changed PIP, but not PIP, photocontrol appears to be at the PIP kinase and phospholipase level. In related studies of the effect of light on phospholipids, 5 min of red irradiation induced significant decreases in phosphatidylcholine and phosphatidylethanola-mine.