Synthesis and in vitro antimicrobial screening of new pyrano[4,3-b]pyrane derivatives of 1H-pyrazole

A new series of pyrano[4,3-b]pyrane 4a-l bearing 1H-pyrazole has been synthesized by one pot base catalyzed cyclocondensation reaction of 1H-pyrazole-4-carbaldehyde la-1,malononitrile 2 and 4-hydroxy-6-methylpyrone 3.All the synthesized compounds were screened against six bacterial pathogens,namely B.subtilis,C.tetani,S.pneumoniae,S.typhi,V.cholerae, E.coli and antifungal activity against,two fungal pathogens,A.fumigatus and C.albicans using broth microdilution MIC method. Some of the compounds are found to be equipotent or more potent than that of commercial drugs,against most of employed strains.     

Solvent-free one-pot synthesis,characterization, antibacterial and antifungal activities of novel spiropiperidinyl-1,2,4-triazolidine-3-thiones

A novel approach towards the synthesis of spiropiperidinyl 1,2,4-triazolidine-3-thiones was proposed, exploiting microwave activation coupled with solvent-free reaction conditions. In search for new leads towards potent antimicrobial agents, we tested all the synthesized compounds for their in vitro antibacterial activity against Bacillus subtilis and Micrococcus luteus and antifungal activity against Aspergillus niger, Candida albicans, Candida-6, and Candida-51. Two of the compounds exerted strong in vitro antibacterial activity against B. subtilis and M. luteus, and all the synthesized compounds were potent against the tested fungal strains.     

3-杂环基硫取代-1,3,4,5-四氢-2-氧代-苯并氮杂衍生物的合成

以芳酰肼为原料,合成了一系列3-巯基-5-芳基-1,2,4-三唑、2-巯基-5-芳基-1,3,4-噁二唑和2-巯基-5-芳基-1,3,4-噻二唑,并通过硫原子对3-溴-2-氧代-苯并氮杂3-位上的亲核取代反应将杂环化合物引入了苯并氮杂的结构当中,合成了32个新的苯并氮杂杂环衍生物.为提高其在有机溶剂中的溶解性,在苯并氮杂的N原子上引入乙酸乙酯和乙酸叔丁酯基取代基,合成了36个新衍生物.所有化合物经质谱、核磁共振谱及元素分析确证了结构并初步测定了抗菌活性.     

3-杂环基硫取代-1,3,4,5-四氢-2-氧代-苯并氮杂衍生物的合成

以芳酰肼为原料, 合成了一系列3-巯基-5-芳基-1,2,4-三唑、2-巯基-5-芳基-1,3,4-噁二唑和2-巯基-5-芳 基-1,3,4-噻二唑, 并通过硫原子对3-溴-2-氧代-苯并氮杂3-位上的亲核取代反应将杂环化合物引入了苯并氮杂的结构当中, 合成了32个新的苯并氮杂杂环衍生物. 为提高其在有机溶剂中的溶解性, 在苯并氮杂的N原子上引入乙酸乙酯和乙酸叔丁酯基取代基, 合成了36个新衍生物. 所有化合物经质谱、核磁共振谱及元素分析确证了结构并初步测定了抗菌活性.     

1,2,3-Triazole incorporated coumarin derivatives as potential antifungal and antioxidant agents

A series of novel ethyl-7-((1-(benzyl)-1H-1,2,3-triazol-4-yl)methoxy)-2-oxo-2H-chromene-3-carboxylates 8a-h as potential antifungal agents were synthesized via click chemistry. The antifungal activity was evaluated against five human pathogenic fungal strains, such as Candida albicans, Fusarium oxysporum, Aspergillus flavus, Aspergillus niger and Cryptococcus neoformans. Compound 8c, 8d, 8e and 8h were found to be equipotent against C. albicans when compared with miconazole and compound 8f was found to be two-fold more active compared with miconazole and equipotent to fluconazole against C. albicans. The coumarin-based triazole derivatives were also evaluated for antioxidant activity and compound 8a was found to be potent antioxidant when compared with standard drug. Furthermore, molecular docking study of the newly synthesized compounds was performed and results showed good binding mode in the active site of fungal C. albicans enzyme P450 cytochrome lanosterol 14α-emethylase. Moreover, the synthesized compounds were also analyzed for ADME properties and showed potential to build up as good oral drug candidates.     

Synthesis and antimicrobial screening of pyrano[3,2-<Emphasis Type="Italic">c</Emphasis>]chromene derivatives of 1<Emphasis Type="Italic">H</Emphasis>-pyrazoles

A new series of twenty four derivatives of pyrano[3,2-c]chromene IVa-x bearing 1H-pyrazole were synthesized by a one pot, base-catalyzed cyclocondensation reaction of 1H-pyrazole-4-carbaldehyde Ia-l, malononitrile II and 4-hydroxycoumarin IIIa-b. All the synthesized compounds were characterized by elemental analysis, FT-IR, ¹H NMR and ¹³C NMR spectral data. All the synthesized compounds were screened against six bacterial pathogens, namely B. subtilis, C. tetani, S. pneumoniae, S. typhi, V. cholerae, E. coli and for antifungal activity against two fungal pathogens, A. fumigatus and C. albicans using the broth microdilution MIC method. Some of the compounds were found to be equipotent or more potent than commercial drugs against most of employed strains, as evident from the screening data.      

Synthesis,antimicrobial and anti-inflammatory activities of some novel 5-substituted imidazolone analogs

In view of potent antimicrobial and anti-inflammatory activities exhibited by 5-substituted imidazolones, a variety of novel imidazolone analogs 3a-l were synthesized by the condensation of different substituted oxazolones 1 with various aromatic amines 2. All the synthesized compounds were screened for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. Several analogs produced good or moderate activities particularly against the tested Gram-positive bacteria Micrococcus luteus and Gram-negative bacteria Pseudomonas aeruginosa and. Meanwhile, compounds 3b and 3c displayed marked antifungal activity against C. albicans. In addition, the in vivo anti-inflammatory activity of the synthesized compounds was determined using the carrageenin-induced paw oedema method in rats. Two of 5-substituted imidazolone derivatives, 3k and 3d show good anti-inflammatory activity. The structures of all the newly synthesized compounds were elucidated using IR, ¹H NMR and ¹³C NMR.     

Antifungal metabolites from Blumea balsamifera

The leaves of Blumea balsamifera afforded icthyothereol acetate, cryptomeridiol, lutein, and beta-carotene. The structures of icthyothereol acetate (1) and cryptomeridiol (2) were elucidated by extensive 1D and 2D NMR spectroscopy, while those of lutein and beta-carotene were identified by comparison with literature data. Antimicrobial tests indicated that 1 has moderate activity against the fungi Aspergillus niger, Trichophyton mentagrophytes, and Candida albicans, while 2 has low activity against A. niger, T. mentagrophytes, and C. albicans. Both compounds have no antimicrobial activity against Psuedomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, and Escherichia coli.     

Synthesis of analogs of amathamide A and their preliminary antimicrobial activity

Syntheses of three non-brominated analogs of amathamide A (1), a natural alkaloid isolated from the Tasmanian marine bryozoan Amathia wilsoni, are described. Antimicrobial activity against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Pseudomona aeruginosa, and Candida albicans was tested. Test results for amathamide A (1) showed a weak activity against C. albicans and E. coli. The three non-natural analogs 2-4 proved to be inactive compounds.     

Synthesis, biological and computational study of new Schiff base hydrazones bearing 3-(4-pyridine)-5-mercapto-1,2,4-triazole moiety

A series of new Schiff base hydrazones (compounds 1-16) were synthesized by condensation reaction of 4-amino-3-(4-pyridine)-5-mercapto-1,2,4-triazole with various aldehydes and/or dialdehydes. The structure of the prepared compounds was confirmed by means of 1H NMR, 13C NMR, UV-vis, IR and elemental analyses. The all prepared compounds were assayed for antibacterial (Escherichia coli and Staphylococcus aureus) and antifungal (Candida albicans) activities by disc diffusion method. The results indicate that all tested compounds did not show any antibacterial activity against E. coli, as gram negative bacteria, and antifungal activity against C. albicans. But the compounds 2, 3, 4, 6 and 8 containing 4-Cl, 4-Me, 4-MeO, 2,4-di-Cl and 2-OH substituted phenyl moiety, respectively, showed good inhibition against S. aureus as compare to standard drugs. The structure of all biologically active compounds has also been theoretically studied by ab initio Hartree-Fock (HF) methods.     

Antimicrobial activity of some new thioureides derived from 2-(4-chlorophenoxymethyl)benzoic acid

We report here the characterisation of eight newly synthesized thioureides of 2-(4-chlorophenoxymethyl)-benzoic acid and the evaluation of the in vitro antimicrobial activity of the new compounds against Gram-positive [Listeria monocytogenes,Staphylococcus aureus, Bacillus subtilis], Gram-negative [Psedomonas aeruginosa,Escherichia coli, Salmonella enteritidis], as well as Candida spp., using both reference and clinical multidrug resistant strains to establish the minimal inhibitory concentration (MIC)values. Our results showed that the tested compounds exhibited specific antimicrobial activities, both concerning the spectrum of antimicrobial activity and the corresponding MIC values, which ranged widely between 1024 and 32 mug/mL, depending on the nature and position of the substituents on the benzene ring. The most active compounds were N-[2-(4-chlorophenoxymethyl)-benzoyl]-N'-(2,6-dichlorophenyl)-thiourea (5 g) and N-[2-(4-chlorophenoxymethyl)-benzoyl]-N'-(4-bromophenyl)-thiourea (5h), which showed a broad spectrum of antimicrobial activity against enterobacterial strains (E. coli and S. enteritidis),P. aeruginosa, S. aureus and Candida spp. All the tested compounds except 5f were highly active against S. aureus (MIC=32 mug/mL), suggesting their possible use in the treatment of MRSA infections. Four of compounds also exhibited antifungal activity (MIC =256-32 microg/mL) against C. albicans, but L. monocytogenes as well as B. subtilis were resistant to all tested compounds. Our studies thus demonstrated that among other biological activities,the thioureides of 2-(4-chlorophenoxymethyl)-benzoic acid also exhibit selective and effective antimicrobial properties that could lead to the selection and use of these compounds as efficient antimicrobial agents, especially for the treatment of multidrug resistant infections.     

Study on the synthesis and antimicrobial activity of novel cationic porphyrins

A novel series of quaternary ammonium cationic derivatives based on tetrapyridyl-porphyrin was synthesized.All the compounds were evaluated for their in vitro antibacterial activities against S.aureus,E.coli and P.aeruginosa,and antifungal activities against C.albicans,where microorganisms were exposed and unexposed to the irradiation.The results revealed that some of these compounds,especially,3a and 4a displayed satisfactory antibacterial activity against Gram-positive bacteria S.aureus and moderate an...     

Synthesis of some oxadiazole derivatives as new anticandidal agents

In this study, 5-[(pyrimidin-2-ylthio)methyl]-1,3,4-oxadiazole-2(3H)-thione (3) was synthesized via the ring closure reaction of 2-(pyrimidin-2-ylthio)acetohydrazide (2) with carbon disulphide. New oxadiazole derivatives 4a-f were obtained by the nucleophilic substitution reaction of compound 3 with various phenacyl bromides. The chemical structures of the compounds were elucidated by IR, 1H-NMR, 13C-NMR and FAB+-MS spectral data and elemental analyses. The newly synthesized derivatives 4a-f were tested in vitro by using a microbroth dilution method against C. albicans (clinical isolate, Osmangazi University, Faculty of Medicine, Eski?ehir, Turkey), C. albicans (ATCC 90028), C. glabrata (clinical isolate, Osmangazi University, Faculty of Medicine, Eski?ehir, Turkey), C. tropicalis (NRRL Y-12968), C. krusei (NRRL Y-7179), C. parapsilosis (NRRL Y- 12696), C. albicans (NRRL Y-12983), C. glabrata (clinical isolate, Anadolu University, Faculty of Science, Department of Biology, Eski?ehir, Turkey). Among these compounds, compound 4a was found to be the most potent derivative (MIC = 0.007-0.06 versus ketoconazole: 0.001-0.007 mg/mL) against Candida species, except C. tropicalis and C. krusei when compared with the standard antifungal ketoconazole.     

Green and Efficient Synthesis of 4‐Heteryl‐Quinolines and Their Antibacterial Evaluations

A green and efficient synthesis of 4‐heteryl‐quinolines ( 9a , 9b , 9c , 9d ), ( 10a , 10b , 10c , 10d ) and ( 11a , 11b , 11c , 11d ) has been described using PEG‐600 as a green solvent. Initially, 4‐chloro‐2‐methylquinolines ( 5a , 5b , 5c , 5d ) on reaction with aromatic heterocyclic thiols ( 6 ), ( 7 ), and ( 8 ) using PEG‐600 at 100°C for 30–40 min resulted in ( 9 ), ( 10 ), and ( 11 ) in good yields. Alternatively, ( 9 ), ( 10 ), and ( 11 ) could also be prepared in dimethylformamide using K2CO3 as base and tetrabutylammonium bromide as phase transfer catalyst at 100°C for 1–2 h. All the compounds were synthesized and characterized by IR, NMR, mass spectroscopy, and 13C NMR analysis. All synthesized compounds were screened for their antibacterial activity against clinical strains that include Gram‐positive (Bacillus subtilis MTCC 121, staphylococcus aureus MLS‐16 MTCC 2940, Micrococcus lutes MTCC 2470, and Staphylococcus aureus MTCC 96) and Gram‐negative bacteria (Candida albicans MTCC 3017, Klebsiella planticola MTCC 530, Escherichia coli MTCC 739, and Pseudomonas aeruginosa MTCC 2453). The results revealed that compounds ( 9a , 9d , 10a , 10c , 11b , and 11d ) exhibited significant antibacterial activity almost equal to the standard drug, that is, Ciprofloxacin.     

SYNTHESIS OF SOME 2-[(BENZAZOLE-2-YL)THIO]-DIPHENYLMETHYLACETAMIDE DERIVATIVES AND THEIR ANTIMICROBIAL ACTIVITY

Some 2-[(benzazole-2-yl)thio]diphenylmethylacetamide[3pc] derivatives were synthesized by reacting 2-chloroacethylaminodiphenylmethane with benzazole-2-thions. The structure elucidation of the compounds was performed by IR, ¹ H NMR, and MS-FAB spectral data.

Antimicrobial activity of the compounds was examined. Some of the compounds have shown similar antifungal activities against C. albicans when compared with ketoconazole. It was also observed that some of these compounds have moderate antimicrobial activity when compared with chloramphenicole.     

Chemical constituents of the methanolic extract of leaves of Leiothrix spiralis Ruhland and their antimicrobial activity

Chemical fractionation of the methanolic extract of leaves of Leiothrix spiralis Ruhland afforded the flavonoids luteolin-6-C-β-D-glucopyranoside (1), 7-methoxyluteolin-6-C-β-D-glucopyranoside (2), 7-methoxyluteolin-8-C-β-D-glucopyranoside (3), 4'-methoxyluteolin-6-C-β-D-glucopyranoside (4), and 6-hydroxy-7-methoxyluteolin (5), and the xanthones 8-carboxymethyl-1,5,6-trihydroxy-3-methoxyxanthone (6), 8-carboxy-methyl-1,3,5,6-tetrahydroxyxanthone (7). Methanolic extract, fractions, and isolated compounds of the leaves of L. spiralis were assayed against Gram-positive (Staphylococcus aureus, Bacillus subtilis and Enterococcus faecalis) and Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Salmonella setubal and Helicobacter pylori) and fungi (the yeasts Candida albicans, C. tropicalis, C. krusei and C. parapsilosis). We observed the best minimum inhibitory concentration values for the methanolic extract against Candida parapsilosis, for the fraction 5 + 6 against Gram-negative bacteria E. coli and P. aeruginosa, and compound 7 against all tested Candida strains. The methanolic extract contents suggest that this species may be a promising source of compounds to produce natural phytomedicines.     

The synthesis and biological evaluation of a series of novel 2-COOC_2H_5/COONa substituted 1,5-benzothiazepine derivatives as antimicrobial agents

A series of novel 1,5-benzothiazepine derivatives containing COOC2H5/COONa groups at the C(2)-position were synthesized and evaluated for their antifungal and antibacterial activities by both disc diffusion and minimal inhibition concentration (MIC) methods. Most of the compounds have been shown to have moderate to good antibacterial activity against S. aureus, S. epidermidis and excellent antifungal activity against C. albicans.     

Novel dihydropyrazole derivatives linked with multi（hetero）aromatic ring： Synthesis and antibacterial activity

Eight novel heterocycle-substituted dihydropyrazole derivatives were synthesized and characterized by ESI-MS,~1H NMR and ~(13)C NMR.All of the compounds have been screened for their antibacterial potential in vitro against Bacillus subtilis, Staphylococcus aureus,Escherichia coli and Pseudomonas aeruginosa.The results show that compounds 9b,9g and 9h displayed significant activity with MIC values in the range of 0.39-1.562μg/mL against B.subtilis.     

Synthesis,antimicrobial, antiquorum-sensing and cytotoxic activities of new series of benzothiazole derivatives

New series of benzothiazole derivatives were designed and synthesized. The newly synthesized compounds were screened for their antibacterial activity against Escherichia coli, Staphylococcus aureus and Bacillus cereus. Compounds 6j and 6o showed the highest activity against E. coli and S. aureus. The antifungal activity of these compounds was also tested against Candida albicans and Aspergillus fumigatus293. Compounds 4c, 4g and 6j exhibited the highest activity against C. albicans. In addition, compounds4 a and 6j displayed promising activity against A. fumigatus 293. The same compounds were examined for their antiquorum-sensing activity against Chromobacterium violaceum ATCC 12472, whereas compounds4 a, 6j and 6p showed moderate activity. The in vitro cytotoxicity testing of the synthesized compounds was performed against cervical cancer(Hela) and kidney fibroblast cancer(COS-7) cell lines. Results indicated that all tested compounds have IC50 values 50 mmol/L against both cell lines. Molecular properties, toxicities, drug-likeness, and drug score profiles of compounds 4a–c, 5a, 6g,h, 6j, 6l, 6o and7 c,d were also assessed.     

Cr(III), Fe(III) and Co(III) complexes of tetradentate (ONNO) Schiff base ligands: synthesis, characterization, properties and biological activity

A series of metal complexes were synthesized from equimolar amounts of Schiff bases: 1,4-bis[3-(2-hydroxy-1-naphthaldimine)propyl]piperazine (bappnaf) and 1,8-bis[3-(2-hydroxy-1-naphthaldimine)-p-menthane (damnaf) with metal chlorides. All of synthesized compounds were characterized by elemental analyses, spectral (UV-vis, IR, (1)H-(13)C NMR, LC-MS) and thermal (TGA-DTA) methods, magnetic and conductance measurements. Schiff base complexes supposed in tetragonal geometry have the general formula [M(bappnaf or damnaf)]Cl.nH(2)O, where M=Cr(III), Co(III) and n=2, 3. But also Fe(III) complexes have octahedral geometry by the coordination of two water molecules and the formula is [Fe(bappnaf or damnaf)(H(2)O)(2)]Cl. The changes in the selected vibration bands in FT-IR indicate that Schiff bases behave as (ONNO) tetradentate ligands and coordinate to metal ions from two phenolic oxygen atoms and two azomethine nitrogen atoms. Conductance measurements suggest 1:1 electrolytic nature of the metal complexes. The synthesized compounds except bappnaf ligand have the antimicrobial activity against the bacteria: Escherichia coli (ATCC 11230), Yersinia enterocolitica (ATCC 1501), Bacillus magaterium (RSKK 5117), Bacillus subtilis (RSKK 244), Bacillus cereus (RSKK 863) and the fungi: Candida albicans (ATCC 10239). These results have been considerably interest in piperazine derivatives due to their significant applications in antimicrobial studies.