Design and synthesis of some azole derivatives as potential antimicrobial agents

Syntheses of 1,2,4-triazol-3-ones, 4a, 4b, and 5 were performed starting from ester ethoxycarbonylhydrazones (1a, 1b) that were reported earlier. The treatment of triazole derivatives, 4a, 4b, and 5 with several sulfonyl halides produced the corresponding sulfonamides, 6–10. Syntheses of carbo(thio)amides, 15, 17, and 18 were carried out by the treatment of (substituted)phenyliso(thio)cyanates with hydrazides 13, 14 which were obtained starting from 4a and 5 by two steps. Cyclization of compounds 15 and 17 in basic media resulted in the conversion of carbo(thio)amide side chain to 5-oxo- or 5-mercapto-1,2,4-triazole ring. Cyclocondensation of 17 with ethyl chloroacetate and 4-nitrophenacylbromide gave 1,3-thiazolidin, 20 and 1,3-thiazol 21, derivatives, respectively. Newly synthesized compounds were screened for their antimicrobial activities, and some of them displayed activity against the test microorganisms. Then the highest activity was observed for compounds 6 and 7 carrying cyclic sulfonamide function beside 1,2,4-triazole nucleus.     

Synthesis of 4-substituted aminoquinoline-3-carboxylates as potential antimicrobial agents

A series of 4-substituted aminoquinoline-3-carboxylates was prepared and evaluated for antimicrobial activity. Four of the compounds (VIII, XIII, XV, and XXIII) exhibited low activity against Staphylococcus aureus.     

New pyridine derivatives as potential antimicrobial agents

A set of pyridine derivatives bearing a substituted alkylthio chain or a piperidyl ring in position 2 or 4 were synthesized, and their antimycobacterial and antifugal activities were evaluated. Chemical structures were confirmed by IR and NMR data, and by elemental analysis. Minimum inhibitory concentrations (MIC) were used for the evaluation of microbiological activity in vitro. The compounds were moderately active against both Mycobacterium tuberculosis and nontuberculous mycobacteria. The most active compound was 2-cyanomethylthiopyridine-4-carbonitrile (7) with MIC against Mycobacterium kansasii in the range of 8-4 mumol/l. The antifungal activities of the compounds were relatively low.     

Synthesis of benzimidazole derivatives as potential antimicrobial agents

Three novel series of benzimidazol derivatives were prepared. Namely; 2-alkyl-1-(4-substituted-4H-1,2,4-triazole-5-thion-3-yl)methylb enzimidazoles; 2-alkyl-1-(5-substituted amino-1,3,4-thiadiazol-2-yl)methylbenzimidazoles; and 2-alkyl-1-[(3,4-disubstituted thiazolin-2-ylidene)hydrazinocarbonyl] methylbenzimidazoles. The antimicrobial testing of the prepared compounds as well as of the key intermediate thiosemicarbazides was performed.     

Synthesis of alkyloxybenzamide derivatives as potential antimicrobial agents

Three series of alkyloxybenzamido derivatives have been prepared. The first comprises N1-[4-(4-alkyloxybenzamido)benzoyl]-N2-substituted alkylidene hydrazine, the second involves 1-[4-(4-alkyloxybenzamido)benzoyl]-4-alkyl, aryl, or aralkyl-3-thiosemicarbazides, and the third includes 1-substituted-5-[4-(4-alkyloxybenzamido)phenyl]-1,3,4-triazole-2-t hione. Representative samples of the prepared compounds were tested for their in-vitro antimicrobial activity.     

Benzimidazolyl quinolinyl mercaptotriazoles as potential antimicrobial and antiviral agents

Condensation of ethylaceto acetate (EAA) with resorcinol in concentrated H2SO4 afforded 7-hydroxy-4-methyl coumarin (1), which on reaction with thiosemicarbazide in anhydrous pyridine yielded 7-hydroxy-4-methyl-quinolinyl [1,5-c]-mercaptotriazole (2). Reaction of 2 with formaldehyde solution and amino acid in ethanol yielded 7-hydroxy-4-methyl-8-(N-methyl-aminoacid)-quinolinyl [1,5-c]-2'-mercaptotriazole (3a-e). Interaction of 3 with o-phenylenediamine in pyridine yielded 7-hydroxy-4-methyl-8-(aminobenzimidazolyl)-quinolinyl [1,5-c]-2'-mercaptotriazole derivatives (4a-e). The latter compounds were evaluated for their antiviral and antimicrobial activities.     

Eco-friendly synthesis of functionalized chitosan-based nanoantibiotic system for potential delivery of linezolid as antimicrobial agents

To obtain a healthy human being with beneficial microflora against different pathogenic infections, classical antibiotics with nanosized biomaterials were used to inhibit the growth of bacterium by their potent synergistic effect. Hence, this study planned to load an oxazolidinone antibiotic named linezolid (LD) onto functionalized chitosan (CN) with 3, 5- dinitrosalyslic acid (DA) via microwave synthesis without harsh condition. The exploring synergistic effect of linezolid (LD) with CN/DA controllable nanostructure was compact efflux-mediated methicillin-resistant Staphylococcus aureus (MRSA) burden and other selected bactericide Gram-positive ((S. aureus), Gram-negative (E. coli), Fungi (C. albicans), Yeast (A. niger), and E. faecalis. The obtained results showed that LD was incorporated into both the internal and external surface of the aggregated CN/DA nanosystem with an average diameter of 150 nm ± 4 hints of the drug loading. Owing to the nature of functionalized CN, the release efficiency attains 98.4% within 100 min. The designed LD@CN/DA exhibited inhibition zone 54 mm, 59 mm, 69 mm, 54 mm, 57 mm, and 24 mm against the tested microbes respectively rather than individual LD. The major target of the current research is achieved by using LD@CN/DA as a nanoantibiotic system that has exceptional consistently active against multi-resistant pathogens, in between MRSA which resist LD. Also, cell viability was performed even after three days of direct cell culture on the surface of the designed nanoantibiotic. The mechanism of microbial inhibition was correlated and rationalized to different charges and the presence of oxygen species against microbial infections. Our findings provide a deep explanation about nanostructured antibiotics design with enhanced potentially pathogen-specific activity.     

Docking simulation, synthesis and biological evaluation of novel pyridazinone containing thymol as potential antimicrobial agents

Novel derivatives of pyridazinone containing thymol have been synthesized and evaluated for their in vitro antimicrobial activity. Antimicrobial activities were determined using agar well diffusion method against the bacterial E. coli and S. aureus and the fungi Aspergillus niger and P. marneffei. Among all the synthesized pyridazinone compounds, IV, Va–c, Vg–l and lV, Va–b, Vg–l showed good bactericidal and fungicidal activity, respectively, than that of thymol itself. Virtual screening was carried out through docking analysis towards glucosamine-6-phosphate synthase and A. niger phytase. Almost all the synthesized compounds exhibited good binding affinity towards receptor with respect to parent itself.     

Synthesis of 4-hydroxycoumarin heteroarylhybrids as potential antimicrobial agents

A new series of 4-hydroxycoumarin derivatives 3a-d was synthesized by the reaction of 3-bromo-4-hydroxy coumarin 1 with various heteroaldehydes 2a-d in good yields. The synthesized compounds were characterized on the basis of their elemental and spectral (IR, (1)H-NMR and mass spectrometry) analysis. All target compounds were evaluated for their in-vitro antimicrobial activity against Streptococcus pyogenes, methicillin-resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumonia, and Escherichia coli bacterial strains and fungal cultures of Candida albicans, Aspergillus fumigatus, Trichophyton mentagrophytes, and Penicillium marneffei by disk diffusion assay with slight modifications. The minimum inhibitory concentration (MIC) was determined for the test compounds as well as for reference standards. Among the tested compounds, 3a has shown the most potent antibacterial as well as antifungal activities.     

Comparative study of conventional and microwave-assisted synthesis of some Schiff bases and their potential as antimicrobial agents

A series of Schiff bases (compounds 1–10) were synthesized by condensing heterocyclic/aromatic aldehydes with heterocyclic/aromatic amines through both, conventional method and microwave-assisted synthesis. The compounds were confirmed by means of IR spectroscopy, Mass spectrometry, ¹H NMR and elemental analyses. The compounds were assayed for antibacterial activity against selected strains of Gram positive, Gram negative bacteria and some fungi by zone inhibition method. Minimum inhibitory concentration (MIC) was also determined for each compound. Reaction times were drastically reduced by microwave-assisted synthesis. MIC was as low as 50 μg/ml exhibited by compounds 2 (against Escherichia coli, Aspergillus niger and Penicillium chrysogenum) and 10 (against Bacillus subtilis). The study presents a series of potential antimicrobial agents through efficient and simple reactions and mild reaction conditions, thereby offering a green chemistry approach.     

Arylidenepyruvic acid thiosemicarbazone and thiazoline derivatives as potential antimicrobial agents

Two novel series of arylidenepyruvic acid thiosemicarbazone and thiazoline derivatives were synthesized and evaluated as potential antimicrobial agents. These substances did not exhibit any significant antibacterial effects when tested against a variety of microorganisms.     

A clubbed quinazolinone and 4-thiazolidinone as potential antimicrobial agents

A series of N-{5-[(2-chlorophenyl)methylene]-2-(4-hydroxyphenyl]-4-oxo(1,3-thiazolidin-3-yl)}{4-[2-(4-methylphenyl)-4-oxo(3-hydroquinazolin-3-yl)]phenyl}carboxamides (6a–n) have been synthesized. All the synthesized compounds were screened for in vitro antibacterial and antifungal activities on Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus pyogenes, Candida albicans, Aspergillus niger, and Aspergillus clavatus. The structures of the compounds were elucidated by IR, ¹H NMR, ¹³C NMR, and Mass spectra.     

Synthesis of some novel quinoline-3-carboxylic acids and pyrimidoquinoline derivatives as potential antimicrobial agents

The synthesis and in vitro antimicrobial evaluation of several quinoline and pyrimidoquinoline derivatives are described. Treatment of 7-substituted quinolin-2(1H)-one-3-carboxylic acids 2a-c with phosphoryl chloride or thionyl chloride gave rise to the 7-substituted 2-chloroquinoline-3-carboxylic acids 3a-c and 7-substituted 2-chloro-3-chlorocarbonylquinolines 5a-c respectively. The 2-chloro function in compounds 3a-c was replaced by 2-aminothiazole or 2-aminopyridine to give 2-(thiazol-2-yl)aminoquinoline-3-carboxylic acids 4a-c or 2-(pyrid-2-yl)aminoquinoline-3-carboxylic acids 4d-f. Treatment of 5a-c with the same heterocyclic amines at room temperature furnished the corresponding 7-substituted 2-chloro-3-heteryl-aminocarbonylquinolines 6a-f. The tetracyclic 9-substituted thiazolo[3', 2':1, 2]-pyrimido[4, 5-b]quinolin-5-ones 7a-c and 10-substituted pyrido[1', 2':1, 2]-pyrimido[4, 5-b]quinolin-6-ones 7d-f were synthesized by heating 5a-c with the heterocyclic amines in toluene or by heating 6a-f under reflux in dimethylformamide. The products were evaluated in vitro for potential antimicrobial activity.     

Novel pyrazole derivatives as potential promising anti-inflammatory antimicrobial agents

Four series of 1H-pyrazole derivatives have been synthesized. The first series was synthesized starting by condensing the hydrazine derivatives 1a-d with 4-(1-ethoxycarbonyl-2-oxopropyl)azobenzoic acid 2a in ethanol or glacial acetic acid to generate the corresponding pyrazoline derivatives 3a-d. Likewise, heating 1a-d with 4-(1-acetyl-2-oxopropyl)azobenzoic acid 2b gave rise to the pyrazole derivatives 4a-d. Similarly, reaction of 1a-d with ethyl 2-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-ylazo)-3-oxobutanoate 2c or 3-(1,5-dimethyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl azo)pentane-2,4-dione 2d in ethanol or glacial acetic acid led to the corresponding pyrazoline derivatives 5a-d or pyrazole derivatives 6a-d. The newly synthesized compounds were evaluated for their anti-inflammatory-antimicrobial activities. In addition, the ulcerogenic and acute toxicity profiles were determined. Compound 6c, proved to be the most active anti-inflammatory-antimicrobial agent in the present study with a good safety margin and no ulcerogenic effect.     

Synthesis of 3-aryl-2-substituted-4(3H)-quinazolines as potential antimicrobial agents

Three new series of 4(3H)-quinazolinone derivatives were synthesized, namely: [3-Aryl-4(3H)-quinazolinon-2-yl]-methylenehydrazino-(N- substituted)-thiocarbamides, 3-Aryl-2-(3-substituted-4-phenyl-2,3-dihydrothiazol-2-ylidenehy drazonomethyl)-4 (3H)-quinazolinones and 3-Aryl-2-(3-substituted-4-oxothiazolidin-2-ylidenehydrazonometh yl)-4(3H)-quinazolinones. The antimicrobial activities of the synthesized compounds were also studied.     

Synthesis and biological evaluation of novel benzoquinones as potential antimicrobial agents

New series of 2,5-dihydroxyphenyl-1,3-thiazoles 4a–l was synthesized by reacting 2,5-dihydroxyphenacyl bromide with various 4-aryl thiosemicarbazones 3a–l that on oxidation with ferric chloride yielded the corresponding N ¹-substituted benzylidene-N ²-[3-aryl-4-(1,4-benzoquinon-2-yl)-1,3-thiazol-2-ylidene]hydrazines 5a–l. They were evaluated for antibacterial activity against Staphylococcus aureus and Bacillus subtilis as Gram-positive bacteria, Escherichia coli and Pseudomonas aeruginosa as Gram-negative bacteria. They were also evaluated for their in vitro antifungal potential against Candida albicans. Almost all tested compounds were found to possess variable degrees of antimicrobial activity. The obtained data revealed that compounds 4b–h and 5e, 5f and 5l exhibited promising antimicrobial activity against the tested organisms of which compound 4b proved to be the most active.     

Synthesis of certain thiosemicarbazide and triazole derivatives as potential antimicrobial agents

Two novel series of thiosemicarbazide derivatives were synthesized: 2-[4-(substituted thiocarbamoylhydrazinocarbonyl) phenoxymethyl]-1H-benzimidazoles and 1-benzyl-2-[4-(substituted thiocarbamoylhydrazinocarbonyl) phenoxymethyl]-1H-benzimidazoles, and cyclised to 2-[4-(4-substituted-4H-1,2,4-triazole-5-thion-3-yl)phenoxymethy ]-1H-benzimidazoles and 1-benzyl-2-[4-(4-substituted-4H-1,2,4-triazole-5- 5-thion-3-yl)phenoxymethyl]-1H-benzimidazoles, respectively. The antimicrobial activity of the prepared compounds was tested.     

Synthesis of certain mercapto-and aminopyrimidine derivatives as potential antimicrobial agents

Reaction of ethyl 4-chloro-2-phenylpyrimidine-4-carboxylate (4) with 5-chloro-2-methylthiophenol or 3-aryl-4-phenyl-1,2,4-triazole-5-thiol yielded the corresponding thioethers (5) and (8a, b), respectively. Careful alkaline hydrolysis of (5) yielded the corresponding carboxylic acid (6). Reaction of (4) withp-aminoacetophenone yielded compound (10) which was reacted with certain aromatic aldehydes to afford the α, β-unsaturated ketones (11a–d). Condensation of (11a–d) with malononitrile or phenylhydrazine yielded the 2-amino-3-cyanopyridines (12a–f) or the 2-pyrazolines (13a, b), respectively. Seven representative compounds were tested for theirin vitro antimicrobial activity against some pathogenic micro-organisms, some of them were proved to be active.     

3-Carbonylacrylic derivatives as potential antimicrobial agents. Correlations between activity and reactivity toward cysteine

A number of 3-carbonylacrylic acid derivatives were prepared, with a view to varying systematically the stereoelectronic environment of the conjugated double bond. The rates of reaction with cysteine were measured spectrophotometrically when possible or by stopped flow when very fast. Some of the final reaction products were isolated. Other properties examined were partition substituent constants and antimicrobial activity. On the basis of published data and these studies, the activity appears to be the combined effect of at least two mechanisms, one probably related to the effect of these structures on surface tension, the other to the electrophilic properties of the unsaturated system.     

Synthesis of certain 2-aminoadamantane derivatives as potential antimicrobial agents

N-(2-Adamantyl)-N'-(5-arylhydrazono-6-methyl-4-oxopyrimidin-2-yl) guanidines (IIIa, b), 2-(2-adamantyl-amino)-4-amino-s-triazine (IVa) and its 6-chloromethyl derivative (IVb) were prepared by cyclization of 1-(2-admantyl) biguanide HCl (I) with ethyl 2-arylhydrazono-3-oxobutyrates (II), ethyl formate and ethyl chloroacetate, respectively. Where 1-(2-adamantyl)-3-(4, 5-dioxo-2-imidazolidinylidene) guanidine (V) was used as intermediate for the synthesis of amides (VIIa, b), hydrazide (VIII) and azomethine derivatives (IXa, b) of alkyl 2-(2-adamantyl-amino)-4-amino-s-triazine-6-carboxylates (VI a, b). The antimicrobial testing of the prepared compounds proved that compound IXb was the most active. It showed a marked bacteriostatic effect againstStaphylococcus aureus andBacillus subtilis.