Synthesis,Characterization, and Antimicrobial Potential of Some 1,4-Disubstituted 1,2,3-Bistriazoles

Abstract

A convenient synthesis of some new 1,4-disubstituted 1,2,3-bistriazoles (3a–3f, 4a–4f, 6a–6b, 7a–7b) is reported via copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddition of various terminal alkynes with 1,4-bis(azidomethyl)benzene and 1,6-diazidohexane. The synthesized compounds were characterized by spectral techniques including infrared, ¹H NMR, ¹³C NMR, and high-resolution mass spectrometry and tested in vitro for antimicrobial potential against Bacillus subtilis and Staphylococcus aureus (Gram-positive bacteria), Pseudomonas aeruginosa and Escherichia coli (Gram-negative bacteria), and Candida albicans and Aspergillus niger (fungi). Among the synthesized 1,4-disubstituted 1,2,3-bistriazoles, compounds 6a, 6b, and 7b displayed excellent antimicrobial potential against most of the tested strains.     

Synthesis,characterization and antimicrobial activity of nalidixic acid derivatives with spirohydantoins

This article presents the synthesis of a series of amides, based on the interaction of several 3-aminospirohydantoins with nalidixic acid. The target compounds were characterized by physicochemical parameters, IR, ¹H and ¹³C NMR spectral data. The antimicrobial activity of the products obtained was determined against Gram-positive bacteria Staphylococcus aureus and Bacillus subtilis, Gram-negative bacteria Escherichia coli, Pseudomonas aeruginosa and Salmonella abony, the yeasts Candida albicans and Saccharomyces cerevisiae and the molds Penicillium chrysogenum and Aspergillus niger. The relationship between structure and biological activity of the products obtained was discussed. It was found that the most effective compounds are tetralin (5f) and indane (5g) derivatives, which exhibit a pronounced antimicrobial activity against both tested Gram-positive and Gram-negative bacteria.

     

Antimicrobial tunicamycin derivatives from the deep sea-derived Streptomyces xinghaiensis SCSIO S15077

Abstract

Tunicamycin E (1), featuring a methyl substitution at C-10′, was isolated from marine-derived Streptomyces xinghaiensis SCSIO S15077 originated from the South China Sea sediment together with six known compounds, tunicamycin B (2), tunicamycin X (3), tunicamycin A (4), streptovirudin D₂ (5), tunicamycin C (6), and tunicamycin C₃ (7). The structure of compound 1 was elucidated by detailed spectroscopic data analyses. All the compounds exhibited strong to moderate antibacterial activity against Gram-positive bacteria Bacillus thuringiensis BT01 and B. thuringiensis W102 with MIC values ranging from 0.008 to 2 μg/mL. Moreover, compounds 1–7 exhibited moderate antifungal activity against Candida albicans ATCC 96901 and C. albicans CMCC (F) 98001 with MIC values ranging from 2 to 32 μg/mL. This is the first report that tunicamycins exhibit antimicrobial activities against B. thuringiensis, C. albicans CMCC (F) 98001 and a fluconazole resistant strain C. albicans ATCC 96901.     

Efficient and convenient synthesis,characterization, and antimicrobial evaluation of some new tetracyclic 1,4-benzothiazines

In the present study, 20 new tetracyclic 1,4-benzothiazines (4a–4 t) were conveniently synthesized in good yields and characterized by different spectral and physical techniques. The in vitro antimicrobial evaluation of the synthesized benzothiazine derivatives was performed by serial dilution against two Gram-positive bacteria [Bacillus subtilis (MTCC 441) and Staphylococcus epidermidis (MTCC 6880)], two Gram-negative bacteria [Escherichia coli (MTCC 1652) and Pseudomonas aeruginosa (MTCC 424)], and two fungal strains [Candida albicans (MTCC 227) and Aspergillus niger (MTCC 8189)]. The derivatives 4 l and 4 t were found to be more potent than standard drug, i.e., fluconazole, against A. niger and C. albicans, respectively.     

Antimicrobial Activities of a Series of Diphenyl (4′-(Aryldiazenyl)Biphenyl-4-Ylamino)(Pyridin-3-YL)Methylphosphonates

Abstract

A series of diphenyl (4′-(aryldiazenyl)biphenyl-4-ylamino)(pyridin-3-yl)methyl- phosphonates 2–7 was synthesized in high yields and their antimicrobial activities were investigated. Some compounds showed high antimicrobial activities against Escherichia coli as a gram-negative bacterium, Bacillus subtilis and Staphylococcus aureus as gram-positive bacteria, and Candida albicans and Schccaromycies cerevisiae as fungi and at low concentrations (10–1000 μg/mL). 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.     

Urea and thiourea derivatives of 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1, 2, 4]triazolo[4,3-a]pyrazine: Synthesis,characterization, antimicrobial activity and docking studies

Abstract

An efficient and robust synthetic procedure was developed primarily for the synthesis of a precursor compound; 3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1, 2, 4]triazolo[4,3-a]pyrazine (11), from 2-chloropyrazine (7) through the chemical transformations such as hydrazine substitution, trifluoroacetyl group induction, cyclization and pyrazine ring reduction. A new series of urea derivatives 13a-e and thiourea derivatives 13f-j of compound 11 have been synthesized and the structures of all the compounds were confirmed using spectroscopic analyses such as IR, ¹H NMR, ¹³C NMR, LC-MS and HRMS. The newly synthesized compounds were screened for their in vitro antimicrobial activity against five bacteria and two fungi, in which compounds 13d, 13i and 13j displayed potential activity against bacterial strains and 13a, 13d, 13g and 13j against fungal strains with the MIC values in the range of 6.25–25.0 µg/mL. An overall comparison of the activity results revealed that thiourea derivatives contain better activity than that of urea compounds. Molecular docking studies on poly (ADP-ribose) polymerase 15 (ARTD7, BAL3) demonstrated that all the synthesized compounds possess significant binding energies (-8.1 to -9.8?kcal/mol) with no adverse effect in the active site of protein.     

Synthesis,Characterization, and Antimicrobial Activity oF The Ligand 3-Methylpyrazole- 4-Carboxaldehyde Thiosemicarbazone and Its Pd(II) Complex

Abstract

The synthesis and characterization of a new palladium(II) complex [Pd(MePhPzTSC)₂] and its corresponding ligand 3-methylpyrazole-4-carboxaldehyde thiosemicarbazone (MePhPzTSC) are described. The bidentate ligand is coordinated to Pd(II) through the azomethine nitrogen atoms and sulfur in the form of thiol by deprotonation of the NH-C = S. The antimicrobial activity of these new compounds was evaluated against gram-negative (Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa) and gram-positive (Staphylococcus aureus and Bacillus thuringiensis) bacteria and two yeast strains (Candida albicans and Saccharomyces cerevisiae). Coordination of the ligand to the metallic ion showed improved antimicrobial activity compared to the free ligand. For the gram-positive bacteria the antimicrobial activity of the complex was higher than that of the positive control used.

[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 following free supplemental files: Additional figures and tables]     

Synthesis and antibacterial activity of some 5-hydroxy-5-trifluoromethyl-4,5-dihydropyrazol-1-thiocarboxamides, 3-trifluoromethylpyrazol-1-thiocarboxamides and 4-aryl-2-(5(3)-trifluoromethyl-1-pyrazolyl)thiazoles

5-Hydroxy-5-trifluoromethyl-4,5-dihydropyrazol-1-thiocarboxamides 3 and 3-trifluoromethylpyrazol-1-thiocarboxamides 4, regioselectively obtained by the condensation of trifluoromethyl-β-diketones with thiosemicarbazide under neutral and acidic conditions, on further reaction with phenacyl bromides 5 afforded 4-aryl-(5-trifluoromethyl-pyrazol-1-yl)thiazoles 6 and 4-aryl-(3-trifluoromethyl-pyrazol-1-yl)thiazoles 7, respectively. Five 4,5-dihydropyrazoles (3a–e) and two pyrazolylthiazoles (6a and 6c) were tested against one Gram-positive and one Gram-negative bacteria to assess their in vitro antibacterial activity. Compounds 3a, 3b and 3e showed moderate antibacterial activity against Gram-positive bacterium, Bacillus pumilus.     

Antifungal activity of cinnamic acid and benzoic acid esters against Candida albicans strains

Candida albicans is an important opportunistic fungal pathogen capable of provoking infection in humans. In the present study, we evaluated the antifungal effect of 23 ester derivatives of the cinnamic and benzoic acids against 3 C. albicans strains (ATCC-76645, LM-106 and LM-23), as well as discuss their Structure–Activity Relationship (SAR). The antifungal assay results revealed that the screened compounds exhibited different levels of activity depending on structural variation. Among the ester analogues, methyl caffeate (5) and methyl 2-nitrocinnamate (10) were the analogues that presented the best antifungal effect against all C. albicans strains, presenting the same MIC values (MIC = 128 μg/mL), followed by methyl biphenyl-2-carboxylate (21) (MIC = 128, 128 and 256 μg/mL for C. albicans LM-106, LM-23, and ATCC-76645, respectively). Our results suggest that certain molecular characteristics are important for the antifungal action.     

New substituted 2-aminomethyl-2-oxo-2λ5-perhydro-[1,3,2]oxazaphospholo [3,4-a]pyridine: Design,synthesis and antimicrobial activity

The synthesis of a new series of P-heterocyclic compounds, substituted 2-aminomethyl-2-oxo-2λ⁵-perhydro-[1,3,2]oxazaphospholo[3,4-a]pyridine derivatives 8(a-j), was accomplished. A key intermediate, 2-(chloromethyl)-2-oxo-2λ⁵-perhydro-[1,3,2]oxazaphospholo[3,4-a]pyridine (6) was primarily synthesized by the condensation of (±)-2-piperidinemethanol (4) and chloromethylphosphonic dichloride (5); subsequently, it was treated with various heterocyclic amines/benzylamines/aminoacid esters, 7(a-j) to obtain the desired products. The structures of the newly synthesized compounds were elucidated by ¹H, ¹³C, and ³¹P NMR spectroscopy, mass spectra and elemental analyses. The biological potency of title products was investigated by screening in vitro antimicrobial activity. The bio-screening data revealed that most of the synthesized derivatives showed potent growth of inhibition against fungi while compared with bacteria. Particularly, compounds 8c and 8i against bacterial strains, and 8a and 8f against fungi exhibited promising activity.     

<Emphasis Type="Italic">Ferula gummosa</Emphasis> Fruits: An Aromatic Antimicrobial Agent

Ferula gummosa Boiss. (Apiaceae) fruit volatile oil was analyzed by GC/MS. Seventy-three components (96.89%) were identified, and the major components were β-pinene (43.78%), α-pinene (27.27%), and myrcene (3.37%). The antimicrobial activity of the oil was tested on three strains of Gram positive bacteria (Staphylococcus aureus, S. epidermis, and Bacillus subtilis), three strains of Gram negative bacteria (Escherichia coli, Salmonella typhi, and Pseudomonas aeruginosa), and two strains of fungi (Candida albicans and C. kefyr). The essential oil remarkably inhibited the growth of the tested microorganisms. The results indicate that the fruits have potential for use as an aromatic antimicrobial agent.__________Published in Khimiya Prirodnykh Soedinenii, No. 3, pp. 252–254, May–June, 2005.     

Different Heterocycles Functionalized s‐Triazine Analogues: Design,Synthesis and In Vitro Antimicrobial,Antituberculosis, and Anti‐HIV Assessment

Some new quinolone condensed s‐triazine derivatives endowed with different heterocycles and 4‐aminobenzonitrile moiety has been synthesized and examined for their bioactivities against eight bacteria (Staphylococcus aureus, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Salmonella typhi, Proteus vulgaris, and Shigella flexneri), two fungi (Aspergillus niger, Candida albicans) by using agar streak dilution method, and Mycobacterium tuberculosis H37Rv by using Lowenstein and Jensen MIC method. Upon preliminary biological screening, it was observed that the majority of the compounds were found to possess a significant broad spectrum antimicrobial (MICs: 6.25–25 µg/mL) and antitubercular (MIC: 12.5 µg/mL) potential. Hence, anti‐HIV activity against two types of HIV viral strains [HIV‐1 (III_B) and HIV‐2 (ROD)] has been carried out using the MTT assay. From this bioassay, we have identified some potent inhibitors acting as anti‐HIV‐1 agents (IC₅₀: 4.45 µg/mL) with promising therapeutic index of 16 for analogue 7 h. The structural assignments of the new products were carried out on the basis of IR, ¹H NMR, ¹³C NMR spectroscopy, and elemental analysis.     

Synthetic,spectral, structural and antimicrobial studies of some Schiff bases 3-d metal complexes

The complexes of tailor made ligands with life essential metal ions may be an emerging area to answer the problems of multi-drug resistance (MDR). The coordination complexes of VO(II), Co(II), Ni(II) and Cu(II) with the Schiff bases derived from 3-bromobenzaldehyde/3-chlorobenzaldehyde with 2-aminophenol have been synthesized and characterized by elemental analysis, molar conductance, electronic spectra, FT-IR, ESR, FAB mass, thermal and magnetic susceptibility measurements, FAB mass and thermal data show degradation of complexes. Both the ligands behave as bidentate coordinating through O and N donor. The complexes exhibit coordination number 4, 5 or 6. X-ray powder diffraction data shows that four (2, 3, 6 and 7) complexes are crystallized in tetragonal system. The in vitro biological screening effects of the investigated compounds were tested against the bacteria Escherichia coli, Staphylococcus aureus and Streptococcus fecalis and the fungi Aspergillus niger, Trichoderma polysporum and Candida albicans by serial dilution method. A comparative study of the MIC values of the Schiff base and their Co(II) (6) and Cu(II) (8) complexes, indicates that the metal complexes exhibit higher or lower antimicrobial activity than the free ligand (L₂).     

Facile synthesis,characterization, and antimicrobial studies of some disubstituted 1,2,3-triazoles with sulfonamide functionality

An expedient synthesis of some 1,4-disubstituted 1,2,3-triazoles (3a–3x) having sulfonamide functionality from various terminal alkynes and aromatic azides through Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition has been reported. The structures of newly synthesized compounds were confirmed by IR, ¹H NMR, ¹³C NMR, high-resolution mass spectra and screened for in vitro antimicrobial activity against Staphylococcus aureus (Gram-positive bacteria), Escherichia coli, Klebsiella pneumoniae, Enterobacter aerogenes (Gram-negative bacteria), Candida albicans, and Aspergillus niger (fungi). Some of the synthesized compounds were found to exhibit good potency against above-tested microbial strains. Moreover, to study the binding interactions, docking simulation of broadly active compound 3x was also performed against E. coli dihydropteroate synthase enzyme.     

Monooxovanadium(V) 2-phenylphenoxides: synthesis,characterization, and antimicrobial potential

Monooxovanadium(V) complexes of the composition VOCl_{3? n} (L) _n (where L = 2-phenylphenoxide ion; n = 1–3) (1–3) have been synthesized in quantitative yields by the reaction of VOCl₃ with 2-phenylphenol in toluene. The characterization of the complexes has been accomplished by elemental analysis, molar conductance measurements, IR, ¹H-NMR, electronic, mass spectral, and thermal studies. The ligands as well as the complexes have been screened for their in vitro antimicrobial activity against the pathogenic bacteria Escherichia coli and Staphylococcus aureus and fungi Candida albicans, Aspergillus niger, and Fusarium oxysporum by a twofold serial dilution. An increase in the biocidal activity was observed for the vanadium complexes. The minimum inhibitory concentration (MIC) values were 6.25–25 µg mL^?1 for complexes, relative to that of the free ligand of 25–50 µg mL^?1.     

Phosphorus-nitrogen compounds part 22. Syntheses, structural investigations, biological activities and DNA interactions of new mono and bis (4-fluorobenzyl) spirocyclophosphazenes

The reactions of hexachlorocyclotriphosphazene, N₃P₃Cl₆, with mono (1 and 2) and bis(4-fluorobenzyl) diamines (3-5), FPhCH₂NH(CH₂)_nNHR (RH or FPhCH₂-), produce mono (1a and 2a) and bis(4-fluorobenzyl) monospirocyclophosphazenes (3a-5a). The tetraaminomonospirocyclophosphazenes (1b-2d) are obtained from the reactions of the partly substituted phosphazenes (1a and 2a) with excess pyrrolidine, morpholine and 1,4-dioxa-8-azaspiro[4,5]decane (DASD), respectively. The tetrachlorobis(4-fluorobenzyl) monospirocyclophosphazenes (4a and 5a) with excess pyrrolidine, morpholine and DASD afford the fully substituted bis(4-fluorobenzyl) monospirocyclophosphazenes (4b, 4d-5d) in boiling THF. In addition, monochlorobis(4-fluorobenzyl) monospirocyclophosphazenes (4e and 4f) have also been isolated from the reactions with excess morpholine and DASD in boiling THF. The structural investigations of the compounds have been verified by elemental analyses, MS, FTIR, ¹H, ¹³C, ¹⁹F (for 1d and 2d), ³¹P NMR, HSQC and HMBC techniques. The crystal structures of 3a, 4a, 5a and 2b have been determined by X-ray crystallography. The compounds 2a-5a, 1b-2d, 4b, 4d-5d, 4e and 4f have been screened for antibacterial effects on bacteria and for antifungal activity against yeast strains. The compounds 1b and 4b showed antimicrobial activity against three species of bacteria, Bacillus subtilis, Bacillus cereus and Staphylococcus aureus, and two fungi, Candida albicans and Candida tropicalis. Minimum inhibitory concentrations (MIC) were determined for 1b and 4b. The MIC values were found to be 5000 μM for each bacteria. The most effective compound, 4b has exhibited activity with a MIC of 312 μM for C. albicans and 625 μM for C. tropicalis. DNA-binding and the nature of the interaction with pBR322 plasmid DNA are studied. All of the compounds induce changes on the DNA mobility and intensity. Prevention of HindIII digestion with the compounds indicates that the compounds bind with AT nucleotides in DNA.     

Synthesis,characterization, and pharmacological aspects of metal(II) complexes incorporating 4-[phenyl(phenylimino)methyl]benzene-1,3-diol

New metallointercalators (1a–1e) have been synthesized using the Schiff base, 4-[phenyl(phenylimino)methyl]benzene-1,3-diol and metal(II) ions, viz. Mn(II), Co(II), Ni(II), Cu(II), and Zn(II). They are characterized by analytical and spectral methods. Elemental analyses and molar conductance values reveal that the Schiff base metal(II) complexes have 1?:?2 stoichiometry and are non-electrolytes. The Schiff base (HL) binds with M(II) ions through azomethine and deprotonated phenolic groups. Thermal studies reveal the presence of water in 1a–1c. Powder X-ray diffraction and SEM studies show that all the complexes are microcrystalline with homogenous morphology. In vitro biological activities of HL and 1a–1e have been screened against bacteria and fungi by well diffusion technique, revealing that these complexes are good antimicrobial agents against various pathogens. The complexes exhibit better biological activities than HL. Complex 1d binds with Calf thymus DNA through intercalation and weak covalent interactions. The oxidative cleavage of 1a–1e with pUC 19 DNA has also been explored. The results indicate that they bind to DNA through intercalation and are efficient metallointercalators and cleaving agents.     

Synthesis and antimicrobial activity of tetrazolo[1,5-a]quinoline-4-carbonitrile derivatives

Abstract  

A series of new tetrazolo[1,5-a]quinoline-4-carbonitrile derivatives were synthesized for the first time via tetrazolo[1,5-a]quinoline derivatives. Elemental analysis, IR, ¹H NMR, ¹³C NMR, and mass spectral data were used to elucidate the structures of all newly synthesized compounds. In vitro antimicrobial activities of synthesized compounds were investigated against Gram-positive Bacillus subtilis, Gram-negative Escherichia coli, and two fungi, Candida albicans and Aspergillus niger, in comparison with standard drugs. Some of the tested compounds showed significant antimicrobial activity.     

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.     

Copper(II) and cobalt(II) complexes of 5-methyl pyrazole-3-carboxylic acid: synthesis,X-ray crystallography,thermal analysis and in vitro antimicrobial activity

Abstract

The coordination behavior of 5-methylpyrazole-3-carboxylic acid (Hmpca) has been demonstrated by the solid state isolation and characterization of [Cu(mpca)₂(H₂O)]·3H₂O (1) [Cu(mpca)₂]·H₂O (2) and [Co(mpca)₂(H₂O)₂] (3). The new compounds are characterized by X-ray crystallography, thermogravimetric analysis and DFT study. The redox properties of the complexes are examined by cyclic voltammetric analysis. The antibacterial and antifungal activities of the compounds against eight bacteria (Escherichia coli, Enterococcus faecalis, Bacillus subtilis, Klebsiella pneumoniae, Proteus vulgaris, Staphylococcus aureus, Pseudomonas aeruginosa and Salmonella typhi) and two fungi (Aspergillus flavus and Candida albicans) are screened using modified agar well diffusion method. The metal complexes demonstrate better inhibition on all bacteria and fungi than the ligand. The high lipophilicity of the complexes accounts for good inhibitory action toward microbes. Among the reported complexes, 3 emerges as an excellent antifungal agent and a better antibiotic than standard fluconazole. The structure and activity relationship indicate that complexes having sufficient Jahn–Teller distortion with high logP values, cross the cell membrane of the microbes creating intercellular damage.