Synthesis and studies on some new fluorine containing triazolothiadiazines as possible antibacterial, antifungal and anticancer agents

Synthesis of a series of 7-arylidene-6-(2,4-dichlorophenyl)-3-aryloxymethyl/anilinomethyl-1,2,4-triazolo[3,4-b]-1,3,4-thiadiazines (3) by the condensation of 3-aryl-1-(2,4-dichloro-5-fluorophenyl)-2-bromo-propen-1-one (1) and 4-amino-5-mercapto-3-aryloxymethyl/anilinomethyl-1,2,4-triazoles (2) is described. The newly synthesized compounds were characterized by elemental analysis IR, 1H NMR and mass spectral data. These compounds were tested for their antimicrobial activities against Escherichia coli, Staphylococcus aureus (Smith), Psuedomonas aeruginosa (Gessard), Bacillus subtilis and Candida albicans. Some of the newly synthesized compounds were also screened for their anticancer activity. Among them compounds 3m, 3o, 3q showed in vitro anticancer activity.     

Synthesis, antimicrobial activity, pharmacophore analysis of some new 2-(substitutedphenyl/benzyl)-5-[(2-benzofuryl)carboxamido]benzoxazoles

The synthesis and antimicrobial activity of a new series of 2-(substitutedphenyl/benzyl)-5-[(2-benzofuryl)carboxamido]benzoxazole derivatives 3-12 were described. The in vitro antimicrobial activity of the compounds was determined against some Gram-positive, Gram-negative bacteria and fungi and their drug-resistant isolates in comparison with standard drugs. Antimicrobial results indicated that the synthesized compounds possessed a broad spectrum of activity with MIC values 500-15.625 microg/ml. In the series, the most active compound against Candida krusei and Candida albicans isolate is 8 with MIC value 31.25 microg/ml. However, it is one dilution less potent than the compared fluconazole. Some of the screened compounds exhibit significant activity, having MIC value as 31.25 microg/ml in Pseudomonas aeruginosa having same activity as Rifampicin. Furthermore, considering the worth of developing new antibacterial agents against drug-resistant P. aeruginosa the present study explores the structure-activity relationship analysis of 2-(substitutedphenyl/benzyl)-5-[(2-benzofuryl)carboxamido]benzoxazoles using 3D-common features pharmacophore hypotheses approach.     

Synthesis and study of antibacterial and antifungal activities of novel 8-methyl-7,9-diaryl-1,2,4,8-tetraazaspiro[4.5]decan-3-thiones

Some novel spiropiperidinyl-1,2,4-triazolidin-3-thiones have been synthesized and studied for their antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa and antifungal activity against Candida albicans, Candida-6, Candida-51, Aspergillus niger and Aspergillus flavus. Compounds 30-32 exhibited potent in vitro antibacterial activity against E. coli and P. aeruginosa whereas the same set of compounds exerted potent in vitro antifungal activity against Candida-6, A. niger and A. flavus.     

Synthesis and study of antibacterial and antifungal activities of novel 1-[2-(benzoxazol-2-yl)ethoxy]- 2,6-diarylpiperidin-4-ones

Some novel benzoxazolylethoxypiperidones have been synthesized and their antibacterial activity against streptococcus faecalis, bacillus subtilis, escherichia coli, staphylococcus aureus aand pseudomonas aeruginosa and antifungal activity against Candida-6, Candida albicans, Aspergillus niger, Candida-51 and Aspergillus flavus were evaluated. Compounds 37, 38 and 39 exerted potent in vitro antibacterial activity against Streptococcus faecalis while compounds 40 and 41 exhibited potent in vitro antifungal activity against Candida-51.     

Synthesis and antimicrobial activities of Schiff bases derived from 5-chloro-salicylaldehyde

A series of Schiff bases (compounds 1-26) were synthesized by reacting 5-chloro-salicylaldehyde and primary amines, 15 (compounds 2-4, 6, 7, 10, 12-17, 23, 25 and 26) of which were first reported. The chemical structures of these compounds were confirmed by means of (1)H NMR, (13)C NMR, ESI-MS and elemental analyses. The compounds were assayed for antibacterial (Bacillus subtilis, Escherichia coli, Pseudomonas fluorescence and Staphylococcus aureus) and antifungal (Aspergillus niger, Candida albicans and Trichophyton rubrum) activities by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl trtrazolium bromide) method. Among the compounds tested, (E)-4-chloro-2-((4-fluorobenzylimino)methyl)phenol (2) showed the most favorable antimicrobial activity with MICs of 45.2, 1.6, 2.8, 3.4, and 47.5 microg/mL against B. subtilis, E. coli, P. fluorescence, S. aureus and A. niger, respectively.     

Synthesis and in vitro microbiological evaluation of imidazo(4,5-b)pyridinylethoxypiperidones

A series of imidazo(4,5-b)pyridinylethoxypiperidones was designed, synthesized and characterized for evaluation of potential antibacterial activity against Bacillus subtilis, Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa and antifungal activity against Candida albicans-6, Candida albicans, Aspergillus niger, Candida albicans-51 and Aspergillus flavus. Structure-activity relationship led to the conclusion that compound 39 exerted strong in vitro antibacterial activity against Bacillus subtilis and Staphylococcus aureus whereas compounds 38 and 39 displayed promising antifungal activity against Aspergillus flavus. The interesting antimicrobial profile of compound 39 led us to select this derivative for further development.     

Synthesis and antimicrobial activity of 4-phenyl/cyclohexyl-5-(1-phenoxyethyl)-3-[N-(2-thiazolyl)acetamido]thio-4H-1,2,4-triazole derivatives

The increasing clinical importance of drug-resistant fungal and bacterial pathogens has lent additional urgency to microbiological research and new antimicrobial compound development. For this purpose, new thiazole derivatives of triazoles were synthesized and evaluated for antifungal and antibacterial activity. The reaction of propionic acid hydrazides with various aryl/alkyl isothiocyanates gave thiosemicarbazides which furnished the mercaptotriazoles by alkali cyclization. The 4-phenyl/cyclohexyl-5-(1-phenoxyethyl)-3-[N-(2-thiazolyl)acetamido]thio-4H-1,2,4-triazole derivatives were synthesized by reacting the mercaptotriazoles with 2-chloro-N-(2-thiazolyl)acetamide. The chemical structures of the compounds were elucidated by IR, 1H-NMR, FAB+-MS spectral data. Their antimicrobial activities against Candida albicans (two strains), Candida glabrata, Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa were investigated. The results showed that some of the compounds have very strong antifungal activity.     

Synthesis and biological activity of some new benzoxazoles

The synthesis and antimicrobial activity of a new series of 5-ethylsulphonyl-2-(substituted-phenyl/substituted-benzyl and/or phenylethyl)benzoxazole derivatives (3a-3t) except 3a, 3g, 3h, 3k [R.S. Pottorf, N.K. Chadha, M. Katkevies, V. Ozola, E. Suna, H. Ghane, T. Regberg, M.R. Player, Tetrahedron Lett. 44 (1) (2003) 175] were described. The in vitro antimicrobial activity of the compounds was determined against some Gram-positive, Gram-negative bacteria, a fungi Candida albicans and their drug-resistant isolates in comparison with standard drugs. Antimicrobial results indicated that the synthesized compounds possessed a broad spectrum of activity with MIC values 250-7.81 microg/ml. While all compounds are less potent than fluconazole against C. albicans, most of them are more potent than fluconazole against C. albicans isolate.     

Synthesis, structure and biological activity of pseudopeptidic macrolides based on an amino alcohol

A series of new pseudopeptidic macrolides 2a-f based on an amino alcohol were synthesized and evaluated for in vitro antibacterial and antifungal activities. The structure-activity relationships of these compounds were studied and the results showed that compounds 2a and 2d exhibited moderate antibacterial activity against Staphylococcus aureus, Bacillus subtilis and Escherichia coli, whereas compound 2e showed potent antifungal activity against all the fungal species tested, showing a promising broad-spectrum antifungal activity. All the compounds have been studied in vitro for the hemolytic activity as a measure of their cytotoxicity, showing that these compounds have low lytic properties.     

Phytochemical and antimicrobial study of an antidiabetic plant: Scoparia dulcis L

The antimicrobial and antifungal effects of different concentrations of chloroform/methanol fractions of Scoparia dulcis were investigated. The isolated fractions were tested against different bacteria like Salmonella typhii, Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa, and Proteus vulgaris and fungal strains such as Alternaria macrospora, Candida albicans, Aspergillus niger, and Fusarium oxysporum. The isolated fractions exhibited significant antimicrobial and antifungal activity against all the tested organisms compared with respective reference drugs. The isolated fractions of S. dulcis showed properties like antimicrobial and antifungal activities that will enable researchers in turn to look for application-oriented principles.     

Synthesis, characterization and structure-activity relationship analysis of novel depsides as potential antibacterials

Twenty-six depsides were synthesized to screen for their antibacterial activity. All of them were reported for the first time. Their chemical structures were clearly determined by (1)H NMR, (13)C NMR, ESI mass spectra and elemental analyses, coupled with one selected single-crystal structure. All the compounds were assayed for antibacterial activities against three gram-positive bacterial strains (Bacillus subtilis ATCC 6633, Staphylococcus aureus ATCC 6538 and Streptococcus faecalis ATCC 9790) and three gram-negative bacterial strains (Escherichia coli ATCC 35218, Pseudomonas aeruginosa ATCC 13525 and Enterobacter cloacae ATCC 13047) by MTT method. Compound 2-(2-methoxy-2-oxoethyl)phenyl 3-nitrobenzoate (C10) and 2-(2-ethoxy-2-oxoethyl)phenyl 3-nitrobenzoate (C23) showed powerful antibacterial activities against B. subtilis with MIC of 0.78 microg/mL while compound 2-(2-methoxy-2-oxoethyl)phenyl 2-(3,4-diethoxyphenyl)acetate (C8) and 2-(2-ethoxy-2-oxoethyl)phenyl 2-(3,4-diethoxyphenyl)acetate (C21) exhibited significant antibacterial activities against E. coli with MIC of 1.562 microg/mL, which were superior to the positive controls penicillin G and kanamycin B, respectively. On the basis of the biological results, structure-activity relationships were discussed.     

Synthesis, crystal structure and antimicrobial activity of deoxybenzoin derivatives from genistein

A series of deoxybenzoin derivatives from genistein were synthesized and their structures were elucidated by (1)H NMR, mass spectral data and micro analyses. The structures of 2, 7 and 10 were determined by single-crystal X-ray analysis. These obtained compounds were evaluated for their assayed antibacterial (Bacillus subtilis, Escherichia coli, Pseudomonas fluorescence and Staphylococcus aureus) and antifungal (Aspergillus niger, Candida albicans and Trichophyton rubrum) activities by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) method. Most compounds have displayed comparable antibacterial activity against bacterial. On the basis of the biological results, structure-activity relationships are discussed.     

Synthesis and antimicrobial activities of 7-O-modified genistein derivatives

Three series of genistein derivatives with heterocycles were prepared, in which genistein and heterocyclic moieties were separated by 2-carbon, 3-carbon and 4-carbon spacers. Among the 33 compounds we prepared 11 of them (2c and 5a-j) are reported for the first time, while the preparation of 2a,b, 3a-j and 4a-j was reported in our recent paper. All the derivatives were screened for antibacterial (Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas fluorescence) and antifungal (Aspergillus niger, Candida albicans and Trichophyton rubrum) activities by MTT method. Among the compounds tested, 4a, 4e, 4f, 4h, 5e and 5f exhibited good antibacterial activities while 4a also showed notable antifungal activity. Especially, 5f exhibited stronger antibacterial activity against B. subtilis and S. aureus comparable to positive controls.     

Synthesis and antimicrobial activity of some novel derivatives of benzofuran: part 1. Synthesis and antimicrobial activity of (benzofuran-2-yl)(3-phenyl-3-methylcyclobutyl) ketoxime derivatives

The reaction of salicylaldehyde with 1-phenyl-1-methyl-3-(2-chloro-1-oxoethyl) cyclobutane (1) and potassium carbonate was used to prepare (benzofuran-2-yl)(3-methyl-3-phenylcyclobutyl) methanone (2) for the starting reagent purposes. (benzofuran-2-yl)(3-phenyl-3-methyl cyclobutyl) ketoxime (3) was synthesized from the reaction of the compound (2) with hidroxylamine. New derivatives of (benzofuran-2-yl)(3-phenyl-3-methyl cyclobutyl) ketoxime (3) such as, O-glycidylketoxime (4) and O-phenylacylketoxime (5a-c) were obtained very high yields. Alkyl, allyl and aryl substituted N-oxime ethers (6a-e) were obtained from the reaction compound 3 and various halogen contained compounds. The syntheses of the compounds (7a-f) were carried out from the reaction of the compound (4) and different amines such as, isopropyl amine, natrium azide, morpholine and piperazine. All of the synthesized compounds were tested for antimicrobial activity against Staphylococcus aureus ATCC 6538, Staphylococcus epidermidis ATCC 12228, Escherichia coli ATCC 8739, Klebsiella pneumoniae ATCC 4352, Pseudomonas aeruginosa ATCC 1539, Salmonella typhi, Shigella flexneri, Proteus mirabilis ATCC 14153 and Candida albicans ATCC 10231. Among the synthesized compounds (benzofuran-2-yl)(3-phenyl-3-methyl cyclobutyl)-O-[2-hydroxy-3-(N-methylpiperazino)] propylketoxime (7d) was found the most active derivative against S. aureus ATCC 6538. The compounds 2, 5b, 6b, 6c, 7b and 7f showed very strong and the same antimicrobial effect against C. albicans ATCC 10231. Similarly (benzofuran-2-yl)(3-phenyl-3-methylcyclobutyl)-O-benzylketoxime 6a showed good antimicrobial effect against C. albicans ATCC 10231. None of the other compounds exhibited activity against the other test microorganisms.     

Synthesis and biological evaluation of novel luteolin derivatives as antibacterial agents

A series of luteolin derivatives 2-20 were prepared, 3-20 of which were first reported. The chemical structures of these compounds were confirmed by means of 1H NMR, ESI-MS and elemental analyses. The compounds were assayed for antibacterial (Bacillus subtilis, Staphylococcus aureus, Pseudomonas fluorescens and Escherichia coli) activities by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl trtrazolium bromide) method. Among the compounds tested, most of them displayed significant activity against the tested strains, and 2-(2,3-dihydrobenzo[b][1,4]dioxin-6-yl)-5-hydroxy-7-(2-(3-morpholinopropylamino)ethoxy)-4H-chromen-4-one (17) showed the most favorable antibacterial activity in vitro with MICs of 1.562, 3.125, 3.125, and 6.25 microg/mL against B. subtilis, S. aureus, P. fluorescens and E. coli, respectively. Structure-activity relationships (SAR) were also discussed based on the obtained experimental data.     

Efficient one-pot preparation of novel fused chromeno[2,3-d]pyrimidine and pyrano[2,3-d]pyrimidine derivatives

Some novel chromeno[2,3-d]pyrimidinone, pyrano[2,3-d]pyrimidine, dihydropyrimidine, pyridopyranopyrimidine?and pyrimidopyranopyrimidine have been synthesized. The structures of target compounds were confirmed by elemental analyses and spectral data. The antimicrobial activity of all the target synthesized compounds were tested against various microorganismst such as Pseudomonas aeruginosa; Staphylococcus aureus (Bacteria), Aspergillus flavus (Fungus) and Candida albicans (Yeast fungus) by the disc diffusion method. In general, the novel synthesized compounds showed a good antimicrobial activity against the previously mentioned microorganisms.     

N- and S-alpha-l-arabinopyranosyl[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles. First synthesis and biological evaluation

First synthesis of N- and S-alpha-l-arabinopyranosyl[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles is described. Antimicrobial screening of two selected regioisomeric compounds against Aspergillus fumigatus, Penicillium italicum, Syncephalastrum racemosum, Candida albicans, Staphylococcus aureus, Pseudomonas aeruginosa, Bacillus subtilis and Escherichia coli are compared.     

Synthesis and structure-activity relationships of new antimicrobial active multisubstituted benzazole derivatives

A series of multisubstituted benzoxazoles, benzimidazoles, and benzothiazoles (5-7) as non-nucleoside fused isosteric heterocyclic compounds was synthesized and tested for their antibacterial activities against various Gram-positive and Gram-negative bacteria and antifungal activity against the fungus Candida albicans. Microbiological results indicated that the synthesized compounds possessed a broad spectrum of activity against the tested microorganisms at MIC values between 100 and 3.12 microg/ml. Structure-activity relationships (SAR) studies revealed that benzothiazole ring system enhanced the antimicrobial activity against Staphylococcus aureus. In these sets of non-nucleoside fused heterocyclic compounds electron withdrawing groups at position 5 of the benzazoles increased the activity against C. albicans.     

Synthesis and QSAR modeling of 2-acetyl-2-ethoxycarbonyl-1-[4(4'-arylazo)-phenyl]-N,N-dimethylaminophenyl aziridines as potential antibacterial agents

The present communication deals with the synthesis of a series of 2-acetyl-2-ethoxycarbonyl-1-[4(4'-arylazo)-phenyl]-N,N-dimethylaminophenyl aziridines. The compounds were synthesized in excellent yields (70-80%) and the structures were established on the basis of consistent IR, (1)H NMR and elemental analysis data. The purity has been ascertained by chromatographic resolution using acetic acid--toluene (6:4v/v) as binary eluent. All the compounds have been tested for their antimicrobial activity against a representative panel of bacteria i.e. Bacillus subtilis, Escherichia coli, Pseudomonas diminuta and Staphylococcus aureus using azinomycin as reference drug. All the synthesized compounds were found to exhibit profound antimicrobial activity.     

Synthesis, stereochemistry and antimicrobial evaluation of some N-morpholinoacetyl-2,6-diarylpiperidin-4-ones

In a search for new leads towards potent antimicrobial agents, an array of novel N-morpholinoacetyl-2,6-diarylpiperidin-4-ones has been synthesized and their in vitro antibacterial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Salmonella typhi and antifungal activity against Candida albicans, Rhizopus sp., Aspergillus niger and Aspergillus flavus were evaluated. Structure and stereochemistry of all the N-morpholinoacetyl-2,6-diarylpiperidin-4-ones have been analyzed using (1)H and (13)C NMR spectroscopic techniques. In all the cases, amide N-CO group is preferentially in coplanar orientation with respect to the dynamically averaged plane of the piperidone ring. Further, all the symmetrically substituted compounds 19, 23, 24, 26 and 27 are expected to adopt half boat conformations while other compounds 20-22 and 25 adopt twist-boat conformations. Structure-activity relationship results for these nine compounds have shown that compounds 26 and 27 exerted excellent antibacterial activity against all the bacterial strains used except 27 against S. aureus. Against C. albicans and A. flavus, compound 24 recorded excellent antifungal activities while against Rhizopus sp., compound 25 showed potent activities. The obtained results may be used as key step for the building of novel chemical compounds with interesting antimicrobial profiles comparable to that of the standard drugs.