Synthesis,antimicrobial, and antioxidant activity of benzofuran barbitone and benzofuran thiobarbitone derivatives

The synthesis of novel series of benzofuran derivatives, containing barbitone moiety, 5-[(2/4-substitutedphenyl)(5-substituted-1-benzofuran-2-yl) methylidene]pyrimidin-2,4,6(1H,3H,5H)-trione (4a–i) and thiobarbitone moiety, 5-[(2/4-substitutedphenyl)(5-substituted-1-benzofuran-2-yl)methylidene]-2-thioxodihydropyrimidin-4,6(1H, 5H)-dione (5a–i) have been reported. The target compounds (4a–i) and (5a–i) were synthesized by the Knoevenagel condensation of (5-substituted-1-benzofuran-2-yl)(2/4-substitutedphenyl) methanone (3a–i) with barbituric acid and thiobarbituric acid, respectively, in acid medium. These compounds were screened for the antimicrobial and antioxidant activities. From antimicrobial activity results it was found that compounds 4a, 5a, 4c, and 5c displayed good antibacterial and antifungal activity against all tested strains. Further, the synthesized compounds were studied for docking on the enzyme, Glucosamine-6-phosphate synthase and the compounds 4c and 5c have emerged has an active antimicrobial agent with least binding energy (?5.27 and ?4.85 kJ mol^?1). Compounds 4e, 4f, 5e, and 5f showed promising free radical scavenging activity and compounds 5a and 5b showed good chelating ability with Fe²⁺ ions.     

In vitro and in silico biological studies of novel thiazolo[3,2-a]pyrimidine-6-carboxylate derivatives

In the present study, we report the synthesis, characterization of new series of thiazolo[3,2-a]pyrimidine-6-carboxylate derivatives 3a–f and 4a–f. The newly synthesized compounds were screened for in vitro antimicrobial and antiviral activities. The probable mode of action of these active compounds was determined through in silico docking study by docking the receptor methionyl-tRNA synthetase and human inosine-5′-monophosphate dehydrogenase (IMPDH) for antibacterial and antiviral activities, respectively. Among the compounds, 4c exhibited excellent in vitro antimicrobial activity against all tested strains with binding and docking energies ?35.6 and ?12.4 kcal/mol, respectively. The antiviral studies were carried out for the selected compounds in which 4a exhibited 73.69 and 54.42 % of inhibition of buffalopox and camelpox viruses, respectively. Furthermore, compound 4a showed minimum docking and binding energy along with the maximum hydrogen/hydrophobic interaction with IMPDH. The study contributes towards identification and screening of potential antimicrobial and antiviral agent’s against the pathogens.     

Synthesis of β-amino carbonyl derivatives of coumarin and benzofuran and evaluation of their biological activity

A series of β-amino carbonyl compounds containing coumarin (4a–h) and benzofuran (6a–i) moieties was synthesized by a three component Mannich reaction of 3-acetyl-2H-chromen-2-one (1) or 1-(1-benzofuran-2-yl) ethanone (5) with p-substituted aromatic aldehydes (2a–g) and aromatic amines (3a–b) in the presence of cerric ammonium nitrate as a catalyst. The newly synthesized compounds were screened for antimicrobial and antioxidant activities. Compounds 4b, 4e, 4f, 6f, 6g, and 6i showed microbial inhibition with minimal inhibition concentration ranging between 0.040 and 0.500 mg/mL, compounds 4b, 4c, 6c, 6e, and 6i showed promising free radical scavenging activity and compounds 4b, 4f, 6c, 6d, and 6h showed good chelating ability with Fe²⁺ ions. The synthesized compounds were studied for docking on the enzyme, glucosamine-6-phosphate synthase to predict the binding affinity and orientation at the active site of the receptor.     

In vitro antimicrobial activity of o-phenylenediamine-tert-butyl-N-1,2,3-triazole carbamate analogs

In an attempt to design and synthesize effective antimicrobial agents using click chemistry, mono- and di-alkyne-substituted monoboc protected o-phenylenediamines were reacted with different substituted aryl azides which yielded 18 new compounds (4a–4k and 5a–5f, 5l). Structures of all newly synthesized compounds were established by ¹H and ¹³C NMR analysis. The intermediate compound 1 was also confirmed by X-ray crystallography. The title compounds were screened for their antibacterial activity against Gram +ve bacteria (Staphylococcus aureus and Enterococcus faecalis), Gram ?ve bacteria (Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa), and their antifungal profile were tested on (Candida tropicalis, Candida albicans, Candida krusei, and Cryptococcus neoformans) as well as on molds such as (Aspergillus niger, Aspergillus fumigatus). The compounds 4k and 5f both showed maximum potency against S. aureus (ATCC 25323) strain with MIC value of 6.25 µg/ml, which is comparable with standard drug ciprofloxacin (MIC 6.25 µg/ml) while remaining compounds showed moderate to weak activity. Further, all compounds showed average antifungal activity in the range of 100–200 µg/ml.     

Synthesis and pharmacological evaluation of pyrazolopyrimidopyrimidine derivatives: anti-inflammatory agents with gastroprotective effect in rats

We report the synthesis of new anti-inflammatory 1,7-dihydropyrazolo[3′,4′:4,5]pyrimido[1,6-a]pyrimidine 5 from aminocyanopyrazole. All compounds were characterized by physical, chemical and spectral studies. Preliminary pharmacological evaluation of the resulting products showed that compounds 5a, b, f (50–100 mg/kg, i.p) are active anti-inflammatory agents in carrageenan-induced rat paw oedema assay, and their effects are comparable to that of acetylsalicylic–lysine (300 mg/kg, i.p.), used as a reference drug. The nature of substituent (Y, R₃) had a pronounced effect on the anti-inflammatory activity. Studies of structure–activity relationships have led to selection of compound ethyl-3,5-dimethyl-7-imino-N ¹-phenyl-1,7-dihydropyrazolo[3′,4′:4,5]pyrimido[1,6-a]pyrimidine-6-carboxylate, 5f which exhibited the most potent anti-inflammatory activity. In addition, the compounds 5a, b, f showed a significant gastroprotective effect against HCl/EtOH-induced gastric ulcer.     

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, DNA affinity, and antimicrobial activity of 4-substituted phenyl-2,2′-bichalcophenes and aza-analogues

A series of bichalcophene monoamidines 4a–f were synthesized from the corresponding mononitriles 3a–f via a direct reaction with LiN(TMS)₂ followed by deprotection with ethanolic HCl (gas). Bichalcophene mononitriles 3a–f were synthesized via palladium-catalyzed coupling reactions. Thus, a Stille coupling reaction was performed to prepare 6-[5-(thiophen-2-yl)furan-2-yl]nicotinonitrile (3e), when 6-(5-bromofuran-2-yl)nicotinonitrile was allowed to react with 2-n-tributyltin thiophene. The tested bichalcophenes showed a wide range of DNA and protein degradation effect as judged from agarose gel and SDS-PAGE, respectively. Bichalcophenes 3a–f and 4a–f have broad-spectrum antibacterial efficacy being highly active against both Gram-positive (Bacillus subtilis and Staphylococcus aureus) and Gram-negative (Pseudomonas aeruginosa, and Escherichia coli) bacterial strains. The antifungal activity of these bichalcophene series against Saccharomyces cerevisiae was demonstrated. The MIC of bichalcophenes 3a–f and 4a–f against various microorganisms was also determined. The tested bichalcophenes mimic SOD like activity and inhibited the superoxide radical generation.     

Synthesis of azabicyclo[4.2.0]octa-1,3,5-trien-8-one analogues of 1H-imidazo[4,5-c]quinoline and evaluation of their antimicrobial and anticancer activities

In search of new and efficient antimicrobial and anticancer agents based on the imidazoquinoline structural framework, a series of novel 7-(1-isobutyl-1H-imidazo[4,5-c]quinolin-4-yl)-7-azabicyclo[4.2.0]octa-1,3,5-trien-8-ones (8a–f) were synthesized from the corresponding 2,4-dihydroxoquinoline derivative through multistep reactions. The structures of these compounds were established by IR, ¹H NMR, ¹³C NMR and mass spectral studies. The 7-(1-isobutyl-1H-imidazo[4,5-c]quinolin-4-yl)-7-azabicyclo[4.2.0]octa-1,3,5-trien-8-one (8a–f) analogues were evaluated for their in vitro antimicrobial activity by serial dilution method minimum inhibitory concentration (MIC). The derivatives 8c, 8e and 8f exhibited excellent antibacterial activity comparable to the parent drug ampicillin with MIC value. Compounds 7a–f and 8a–f were also assessed for their cytotoxic activity (IC₅₀) against HeLa cells using the Trypan blue exclusion assay method. The compounds 7c and 8b displayed potential anticancer activity. In a molecular docking study, these compounds showed minimum binding energy and good affinity towards the active pocket. They are believed to be good inhibitors of β-tubulin. The results of these studies provided evidence that 7-(1-isobutyl-1H-imidazo[4,5-c]quinolin-4-yl)-7-azabicyclo[4.2.0]octa-1,3,5-trien-8-one (8a–f) derivatives are a promising class of antibacterial and anticancer agents.     

A new class of bactericidal agents against S. aureus,MRSA and VRE derived from bisindolylmethane

A series of bisindolylmethanes (BIMs) (1a–7j) including hybrid BIMs 6a–6c were prepared for bioevaluation. The results of initial antimicrobial screening of compounds 1a–6c showed compounds 2b, 2m, 4a and 5b to be the most potent inhibitors, exhibiting MIC as well as MBC values equal to or less than that of ciprofloxacin (0.5–2 μg/mL) against Staphylococcus aureus, MRSA and VRE. Compound 2m was selected further to study the effect of N,N′ disubstitution towards antibacterial and antitumor activity. It was observed that substitution at N,N′ position (7a–7j) of 2m diminishes its antibacterial activity though in vitro antitumour activity against a panel of prostate, cervical and lung cancer cell lines remains more or less intact.     

Synthesis of new oxadiazole derivatives as anti-inflammatory, analgesic, and antimicrobial agents

In search of pharmalogically active molecules in the class of oxadiazoles, the present article deals with the synthesis of 5-(5′-fluoro-2′-methoxybiphenyl-3-yl)-1,3,4-oxadiazol-2(3H)-one 2 from its hydrazide analog 1. The compound 2 was regioselectively N-alkylated with alkyl halides and produced the compounds 3a–f. Compound 3f was further functionalized with substituted benzenesulfonyl chlorides to give compounds 3g–j. The synthesized compounds were characterized by elemental and spectral analysis. Newly synthesized compounds were tested for their in vivo anti-inflammatory, analgesic, and in vitro antimicrobial activities. The compounds 3a–c were found to have promising anti-inflammatory and analgesic activities. Compounds 3b, 3f, and 3g showed significant antibacterial and antifungal activities.     

Eco-friendly synthesis and antimicrobial activities of substituted-5-(1H-indol-3-yl)methylene)-2,2-dimethyl-1,3-dioxane-4,6-dione derivatives

l-Tyrosine is an efficient catalyst for the condensation of substituted indole-3-aldehydes 1(a–d), N-methyl indole-3-aldehydes 4(a–d), and N-ethyl indole-3-aldehydes 6(a–d) with meldrum’s acid (2) containing a cyclic active methylene group to produce 3(a–d), 5(a–d), and 7(a–d), respectively, in water at room temperature for 30 min. The antimicrobial activities of 3(a–d), 5(a–d), and 7(a–d) have been studied.     

5-phenyl-1-benzofuran-2-yl derivatives: synthesis, antimicrobial, and antioxidant activity

Previously unknown biphenyl containing 5-phenyl-1-benzofuran-2-yl derivatives; methanones (2a–i), tertiary alcohols (3a–l), and carbinols (4a–f) were synthesized and evaluated for their antimicrobial and antioxidant activities to study the effect of functionalization at the carbonyl carbon and substitution at biphenyl ring on these activities. The introduction of hydroxyl group at carbonyl carbon enhanced the antioxidant property (3a, 3g, 3h, 4a, and 4b), while antimicrobial activity decreased; the carbinol and tertiary alcohols corresponding to methanone 2a and 2b showed no antimicrobial activity. Biphenyl methanones 1, 2a, 2f, and 2g exhibited antimicrobial activity with minimal inhibitory concentration ranging between 0.001 and 0.500 mg/mL, tertiary alcohols 3a, 3g, and 3h and carbinols 4a and 4b exhibited the promising antioxidant property. The mode of action of these active compounds was carried out by docking of receptor GlcN6P synthase with newly synthesized candidate ligands 1, 2a, 2e, 2f, 2g, 2h, 3a, 3g, 3h, 4c, and 4d.     

Synthesis and characterization of flurbiprofen hydrazide derivatives as potential anti-HCV, anticancer and antimicrobial agents

A novel series of new flurbiprofen hydrazide derivatives 2-(2-fluorobiphenyl-4-yl)-N′-[(substituted phenyl/5-nitro-2-furyl)methylene]propanehydrazide (3a–k), 2-(2-fluorobiphenyl-4-yl)-N-(2-substituted-4-oxo-1,3-thiazolidine-3-yl)propanamide (4a–b, 4d–k), 2-[2-(2-fluorobiphenyl-4-yl) propanoyl]-N-substituted hydrazinecarbothioamide (5a–h) and 2-(2-fluorobiphenyl-4-yl)-N′-[(3-methyl-4-oxo-1,3-thiazolidin-2-ylidene]propanehydrazide (6a–b, 6e and 6g) has been synthesized in this study. All synthesized compounds were screened for antimicrobial activity against various bacterial and fungal strains. Additionally, compounds were evaluated for the ability to inhibit Hepatitis C virus NS5B polymerase. The most active 4-thiazolidinone compound was 4k (SGK119) with 67.0 % and thiosemicarbazide compound was 5d (SGK123) with 69.50 % inhibition at 200 μM against hepatitis C virus NS5B RNA polymerase. Anticancer activity of the selected compounds (3i, 3j, 3h, 4d, 4i and 6b) was determined at a single dose towards the full panel of 60 human cancer cell lines by the National Cancer Institute (NCI). 2-(2-Fluoro-4-biphenylyl)-N-[2-[4-(trifluoromethyl)phenyl]-4-oxo-1,3-thiazolidine-3-yl]propanamide 4d, containing thiazolidinone ring, demonstrated the most marked effect with 20.80 % growth percent on leukaemia cancer cell line SR at 10^?5 M. The results demonstrated that none of the compounds tested have anticandidal and antifungal activities, but two of them (4a and 4i) showed antibacterial inhibition against Micrococcus luteus, and Staphylococcus cohnii and Staphylococcus aureus, respectively.     

Microwave-assisted synthesis of novel 4H-chromene derivatives bearing 2-aryloxyquinoline and their antimicrobial activity assessment

A new series of 4H-chromene derivatives 6a–x bearing 2-aryloxyquinoline nucleus have been synthesized under microwave irradiation by reaction of 2-aryloxyquinoline-3-carbaldehyde 3a–l, malononitrile 4, and compounds (Cyclohexanedione, Dimidone) 5a–b in the presence of NaOH as the basic catalyst. All the compounds were screened against three Gram-positive bacteria (Streptococcus pneumoniae, Clostridium tetani, Bacillus subtilis), three Gram-negative bacteria (Salmonella typhi, Vibrio cholerae, Escherichia coli) and two fungi (Aspergillus fumigatus, Candida albicans) using the broth microdilution MIC (Minimum Inhibitory Concentration) method. Upon study of the antimicrobial screening, it has been observed that a majority of the compounds were found to be active against C. tetani and B. subtilis as well as against C. albicans as compared to the standard drugs.     

Synthesis, physicochemical properties, antimicrobial and antioxidant studies of pyrazoline derivatives bearing a pyridyl moiety

A series of new pyrazoline compounds bearing a pyridyl moiety (4a–i) were synthesized by condensing appropriate chalcones with hydrazine hydrate and tested for antimicrobial and antioxidant activities. According to in vitro antimicrobial activity against Bacillus subtilis, Staphylococcus epidermidis, Proteus vulgaris, Pseudomonas aeruginosa, Aspergillus niger and Penicillium chrysogenum and antioxidant activity by DPPH method, the compounds 4a, 4d, 4i and 4e, 4f, 4h showed maximum antimicrobial and antioxidant activities, respectively. Physiochemical properties and Lipinski’s ‘Rule of Five’ analysis predicted higher intrinsic quality of the synthesized compounds and revealed that these compounds have good bioavailability and druglikeness properties.     

Synthesis and QSAR studies of some novel disubstituted 1,2,4-triazoles as antimicrobial agents

Disubstituted 1,2,4-triazoles 3a–k, 4a–k, and 6a–k have been synthesized from anthranilic acid and nicotinic acid, respectively, through a multi-step reaction sequence via their hydrazides. Synthesized compounds were evaluated for their in vitro antimicrobial activity against two gram-positive bacteria (S. aureus and B. subtilis), three gram-negative bacteria (E. coli, S. typhi, and K. pneumonia) as well as four fungi (A. niger, A. fumigatus, A. flavus, and C. albicans). To explore computational approach, structure–activity relationships were generated statistically using the synthesized compounds and their respective quantitative values of biological activities. These models can be used in future for predicting antimicrobial activity on similar class of compounds.     

Schiff’s base derivatives bearing 2-thiophenoxyquinoline nucleus as new antibacterial agents

A series of new Schiff’s base derivatives 4a–x bearing 2-thiophenoxyquinoline nucleus have been designed and synthesized by reaction of 2-thiophenoxyquinoline-3-carbaldehydes 2a–d with various benzohydrazides 3a–f in the presence of Ni(NO₃)₂·6H₂O as a catalyst. In vitro antibacterial screening was carried out against two Gram-positive bacteria (Bacillus subtilis ATCC 6633 and Staphylococcus aureus ATCC 6538) and two Gram-negative bacteria (Escherichia coli ATCC 35218 and Pseudomonas aeruginosa ATCC 13525). Of the compounds studied, compound 4e showed chief activity (MIC = 3.13 μg/mL) against S. aureus, and compounds 4p, 4k, and 4w were found to possess effective antibacterial activity against employed strains compared with standards used. The structures of Schiff’s base derivatives were established by using various spectroscopic methods. A crystal structure of compound 4k has been determined by X-ray diffraction analysis.     

Synthesis, anti-inflammatory and anticancer activity evaluation of some mono- and bis-Schiff’s bases

Several mono-Schiff’s bases (3a–i) and bis-Schiff’s bases (5a–f) were synthesized using microwave irradiation technique (3a–h, 5a–c) and by simply grinding at room temperature for a few minutes (3i, 5d–f). All these compounds were characterized by spectroscopic means and elemental analysis. They were screened for anti-inflammatory and anticancer activities (against five human cancer cell lines). Compound 5f exhibited good anti-inflammatory and compounds 3f, 5a–f exhibited good anticancer activity.     

An efficient synthesis,characterization, and antimicrobial screening of tetrahydropyrimidine derivatives

Several new substituted 1,2,3,4-tetrahydropyrimidine derivatives 2a–h have been synthesized by the modified Biginelli and Hantzsch reactions and compounds were characterized by spectral techniques. All compounds were evaluated for their in vitro antimicrobial activity against different strains of Gram-negative (E. coli and P. aeruginosa) and Gram-positive (S. aureus and S. pyogenus) bacteria and selected fungi C. albicans, A. niger, and A. clavatus using serial Broth dilution method (Mueller–Hinton broth dilution method). Compound 2e was found active against both Gram-negative and -positive bacterial strains used for present study, while compound 2b was good active against Gram-negative and S. pyogenus bacterial strains. Compounds 2a–h were not that much significant against (C. albicans, A. niger, and A. clavatus) selected fungal strains.     

Synthesis of some novel C-5 and N-3 substituted 2-(2-hydroxyphenylimino)thiazolidin-4-one derivatives with broad-spectrum antimicrobial activity

In the present article, compounds 5-((substituted-2-chloroquinolin-3-yl)methylene)-2-(2-hydroxyphenylimino)thiazolidin-4-ones (3a–k), 1-(2-(2-(2-hydroxyphenylimino)-4-oxothiazolidin-3-yl)-2-oxoethyl)pyrimidine-2,4,6(1H,3H,5H)-trione (6) and 1-(2-(5-((substituted-2-chloroquinolin-3-yl)methylene)-2-(2-hydroxyphenylimino)-4-oxothiazolidin-3-yl)-2-oxoethyl)pyrimidine-2,4,6(1H,3H,5H)-triones (8a–k) have been synthesized by substituting C-5 and N-3 position of parent compound 2-(2-hydroxyphenylimino)thiazolidin-4-one (1). Structures of the newly synthesized compounds were assigned on the basis of elemental analyses, IR, ¹H NMR, ¹³C NMR, and mass spectra. In vitro antimicrobial activity of target compounds (3a–k, 6 and 8a–k) was investigated against two Gram-positive, two Gram-negative bacteria and three fungal strains. Among the tested compounds (3e), (3f), and (3h) showed very good antifungal activity, while compound (6) showed very good antibacterial activity. Compounds (8e), (8f), and (8h) showed excellent antifungal and antibacterial activities.