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.     

Synthesis and evaluation of biological and nonlinear optical properties of some novel 2,4-disubstituted [1,3]-thiazoles carrying 2-(aryloxymethyl)-phenyl moiety

A series of 2,4-disubstituted-[1,3]-thiazoles (4a–p and 6a–l) was synthesized from 2-(aryloxymethyl)benzoic acids (1a–d) through a multistep reaction sequence in good yield. The structures of the new compounds were established on the basis of their elemental analyses, IR, ¹H-NMR, ¹³C-NMR and mass spectral data. All the synthesized compounds were screened for their antimicrobial and anti-inflammatory activities. Preliminary results indicated that some of them exhibit promising activities and they deserve more consideration as potential antimicrobial and anti-inflammatory agents. The nonlinear optical (NLO) property of 4a–p was also studied. The compound 4n with 2-(3-methylphenoxymethyl)phenyl and 4-nitrophenyl substituents showed very good NLO property compared to other compounds and also the reference compound, urea.     

Synthesis, characterization, anticancer, and antioxidant activity of some new thiazolidin-4-ones in MCF-7 cells

There are limited studies centring on the potential of thiazolidin-4-ones as anticancer agents. In this study, a new series of 2-(3-substituted-1H-pyrazol-4-yl)-3-(3-substituted-5-sulfanyl-1,2,4-triazol-4-yl)-1,3-thiazolidin-4-one (4a–o) have been synthesized by cyclo-condensation reaction of 5-substituted-4-[(3-substituted-1H-pyrazol-4-ylmethylidene)amino]-2H-1,2,4-triazole-3-thione (3a–o) and thioglycolic acid. The structures of all the synthesized compounds were confirmed by elemental analysis, spectral techniques like IR, ¹H NMR, and mass spectroscopy. Few compounds exhibited dose-dependent cytotoxic effect in MTT assay in human breast cancer (MCF-7) cells. Apoptotic degradation of DNA due to action of potent thiazolidin-4-ones was analysed by agarose gel electrophoresis and visualized by ethidium bromide staining (comet assay). A concentration-dependent increase in tail length and olive tail moment was observed when treated with thiazolidin-4-ones. In vitro antioxidant studies like DPPH and ABTS-free radical scavenging assays-indicated moderate activity of thiazolidin-4-ones.     

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.     

Synthesis and anticonvulsant activity of some new series of pyrrole derivatives

A new series of compounds 3a–f were synthesized from condensation method. Newly synthesized compounds were established by IR, ¹H NMR, ¹³C NMR, mass spectral and elemental analysis. Synthesized compounds 3a–f were screened for anticonvulsant activity. The compound 2,2′-({3-methyl-5-[2-phenylethenyl]-1H-pyrrole-2,4-diyl}dicarbonyl)dihydrazinecarbothioamide 3a showed significant activity compared with other compounds 3b–f against pentamethylene tetrazole-induced seizures.     

Newer thiazolopyrimidine-based sulfonamides clubbed with benzothiazole moiety: synthesis and biological evaluation

A new class of thiazolopyrimidine-based sulfonamides (5a–j) was synthesized from a parent compound 2-methoxy benzoic acid by multistep reaction in order to find new agents to fight against microbial infections. Substituted thiazolopyrimidines (3a–e) were prepared by cyclocondensation of substituted thiazolidinediones (2a–e) with urea in the presence of acid catalyst P₂O₅. Finally, desired compounds (5a–j) were synthesized from intermediates (4a–e) prepared from compounds (3a–e) by chlorosulfonation followed by condensation with corresponding benzothiazole moiety. The synthesized compounds were characterized by IR, ¹H-NMR, ¹³C-NMR spectral data, and elemental analysis, and were evaluated for in vitro antimicrobial activity against certain bacterial and fungal strains using the broth microdilution method as well as antitubercular activity against H₃₇Rv using Lowenstein–Jensen agar method.     

Synthesis and antimicrobial evaluation of 1,3,4-oxadiazole-based chalcone derivatives

A series of chalcones-bearing 1,3,4-oxadiazole derivatives was synthesized as novel bio-active antimicrobial agents against multidrug-resistant bacteria and fungi. The lead compounds (Z)-2-(5-(3-nitrophenyl)-1,3,4-oxadiazol-2-ylthio)-N-(4-(3-(aryl)acryloyl)phenyl)acetamides 5a–n were synthesized via acid-catalyzed aldol condensation (SOCl₂) by reacting N-(4-acetylphenyl)-2-(5-(3-nitrophenyl)-1,3,4-oxadiazol-2-ylthio)acetamide (4) with differently substituted aldehydes. Compound (4) was obtained by reacting 5-(3-nitrophenyl)-1,3,4-oxadiazole-2-thiol (2) with N-(4-acetylphenyl)-2-chloroacetamide (3) in the presence of K₂CO₃. The intermediates (2) and (3) were synthesized simultaneously from 3-nitrobenzohydrazide (1) and 4-aminoacetophenone, respectively. The formation of intermediates and targeted compounds were confirmed for their structure by means of various spectral–analytical techniques like IR, ¹H NMR, ¹³C NMR, elemental analysis, and mass spectra. Antimicrobial properties of all the synthesized compounds have been evaluated against broad panel of bacteria and fungi.     

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.     

Synthesis, characterization, and biological evaluation of thiazolidine-2,4-dione derivatives

As a part of our continuation studies in developing new derivatives as dual antimicrobial/antitumor agents we describe the synthesis of new (Z)-2-(5-arylidene-2,4-dioxothiazolidin-3-yl) acetic acid derivatives (3a–m). The chemical structures of the compound were elucidated by FTIR, ¹H NMR, ¹³C NMR, and elemental analysis data. The antimicrobial activity of all products was examined. All newly synthesized compounds were tested for their in vitro anticancer activity against four cancer cell lines. Among the synthesized compounds, 3a exhibited notable activity against HeLa, HT29, A549, and MCF-7 cell lines with IC₅₀ values of 55, 40, 38, and 50 μM, respectively. In order to predict the drug likeliness of the synthesized compounds on the guidelines of Lipinski rule of five studies was carried out using Pallas software.     

Synthesis and antimicrobial activity of bischalcone derivatives

Several bischalcones (2a–h and 5a–e) and flavones (3a–f) were synthesized and evaluated for their antimicrobial actions. Bischalcones were prepared by condensing 1,1′-(4,6-dimethyl-1,3-phenylene)diethanone (1) or 1-(5-acetyl-2,4-dimethoxyphenyl)-1-ethanone (4) with arylaldehydes. Bischalcones were cyclized in presence of iodine to give corresponding flavones (3a–f). An alternative route to synthesize the flavones consisted in preparing the diester derivatives (6a–f) of (1) with different aromatic acids, which could be converted to β-diketones followed by cyclization to give the corresponding flavones. However, all the attempts in this direction were unsuccessful and it could not be possible to proceed beyond diester stage; six diester derivatives (6a–f) were synthesized. The structures of the synthesized compounds were assigned on the basis of ¹H NMR, mass spectral data and microanalyses results. The antimicrobial screening was performed at a concentration of 100 μg/mL by cup plate method; the compounds inhibiting growth of one or more of the microorganisms were further tested for their minimum inhibitory concentration (MIC) by turbidity method. Preliminary antimicrobial results revealed that the compounds 2a–h and 3a–f were significant in their antibacterial and antifungal activities. MICs results showed that the compound 2f exhibited very good activity against E. coli, P. aeruginosa, and C. albicans with MIC-12.5 μg/mL. Similar type of activity was shown the compound 3a against S. aureus and C. albicans with MIC-12.5 μg/mL. Another compound, 3f, was active against P. aeruginosa and C. albicans with MIC-12.5 μg/mL. Methylation of the two chelated hydroxyls (5a–e) significantly reduced the activity. However, oxidative cyclization of bischalcones resulted in compounds (3a–f) which were found to be considerably active. Diesters (6a–f) were insignificant in their antimicrobial activities.     

New 4-thiazolidinones from 5-ethyl pyridine-2-ethanol: their antibacterial,antifungal, and antitubercular activity

New thiazolidinones 5a–o were prepared from Schiff base 4a–o and thioglycolic acid in the presence of ZnCl₂ from 4-[2-(5-ethylpyridin-2-yl)ethoxy]benzaldehyde. The structures of the synthesized compounds were assigned on the basis of elemental analysis, IR, ¹H NMR ¹³C NMR, and mass spectral data. All the compounds were screened against different strains of bacteria and fungi. Compounds 4e, 4n, 4m, 4o, 5e, 5f, 5j, and 5m possessed very good activity against bacterial and fungal species. These active compounds impelled us to study their antitubercular activity. Schiff base 4n and 4e showed M. tuberculosis MIC value 25 and 62.5 μg/ml, respectively. Thiazolidinone 5m displayed M. tuberculosis MIC at 25 μg/ml, which is better antitubercular activity compared with rifampicin.     

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.     

Microwave-assisted synthesis and antimicrobial screening of new imidazole derivatives bearing 4-thiazolidinone nucleus

A new series of compounds 2-((1-(4-(4-arylidene-2-methyl-5-oxo-4,5-dihydro-1H-imidazol-1-yl)phenyl)ethylidene)hydrazono)thiazolidin-4-ones (4a–o) have been synthesized under conventional and microwave irradiation method. All compounds were characterized by IR, ¹H NMR, ¹³C NMR and mass spectra. Newly synthesized compounds were screened for their antibacterial and antifungal activities on Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Staphylococcus pyogenes, Candida albicans, Aspergillus niger and Aspergillus clavatus by bioassays, namely serial broth dilution. The synthesized compounds showed potent antimicrobial activity against tested microorganisms. Compounds 4h, 4j, 4m and 4n were the most potent amongst tested compounds.     

Synthesis, antioxidant, and antibacterial studies of phenolic esters and amides of 2-(1-benzofuran-2-yl) quinoline-4-carboxylic acid

A new series of phenolic esters 2(a–j) and amides 3(a–c) of 2-(1-benzofuran-2-yl) quinoline-4-carboxylic acid were synthesized by the reaction of 2-(1-benzofuran-2-yl)-quinoline-4-carboxylic acid (1) with various substituted phenols and secondary amines using ethyl-(N′,N′-dimethylamino)propyl carbodiimide hydrochloride (EDC.HCl) as a coupling agent. The newly synthesized compounds were evaluated for in vitro antioxidant and antibacterial activity. Among all tested compounds 2a, 2c, 2e, and 2h showed good chelating ability with Fe⁺² ions, whereas compounds 2g and 2j exhibited good scavenging activity with DPPH free radicals. Concerning antibacterial activities compounds 2a, 2b, 2c, and 2h were found to be equipotent to ampicillin against Enterococcus sp and Staphylococcus aureus, while compound 2e is found to be as potent as ampicillin against Pantoea Dispersa and Ochrobactrum sp. amide derivatives 3(a–c) were found to be less potent when compared to standard.     

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.     

Synthesis,characterization, and antibacterial activities of some novel N,N′-disubstituted thiourea, 2-amino thiazole,and imidazole-2-thione derivatives

In the search of bioactive molecules, a series of novel N-substituted thiourea derivatives 3(a–d) are prepared by reaction of the α-amino pyridyl ketone hydrochloride (2a) with the corresponding aryl isothiocyanates. The synthesis of some new 2-amino thiazoles 4(a–d) and imidazole-2-thiones 6(a–d) were attempted by intramolecular cyclization reaction of the N,N′-disubstituted thioureas 3(a–d) and their intermediate ketals 5(a–d) in diluted aqueous acidic and strong acidic mediums. The structure of all newly synthesized compounds was established by analytical and spectral data. The antibacterial studies to all of the synthesized compounds against Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, and Enterococcus faecalis bacteria with Gram-positive and negative strains, as MIC values are reported. Some of these compounds such as 3a,b,d and 4b,d exhibited a good to significant antibacterial activity. Also, all of new synthesized compounds 3,4,6(a–d) were active against Gram-positive S. aureus bacterium. Thus, some of these compounds can emerge as a promising tool for further research work.     

Synthesis, antitumor activity, and structure–activity relationship of some 4H-pyrano[3,2-h]quinoline and 7H-pyrimido[4′,5′:6,5]pyrano[3,2-h]quinoline derivatives

Several 4H-pyrano[3,2-h]quinoline (3a–d, 4a, 7a,b, 9a–c, 10a,b, 11a,b, and 13a–c) and 7H-pyrimido[4′,5′:6,5]pyrano[3,2-h]quinoline derivatives (8a–c) were obtained by treatment of 8-hydroxyquinoline (1a) and 8-hydroxy-2-methylquinoline (1b) with α-cyano-p-chloro/bromocinnamonitrile (2a,b) or 4H-pyrano[3,2-h]quinoline derivatives (3a,c,d) with different electrophilic reagents followed by nucleophilic reagents. Structures of these compounds were established on the basis of spectral data. The antitumor activity of the synthesized compounds was investigated in comparison with Vinblastine. Among them, compounds 3c,d, 4a, 8b, 9b,c, 11a,b, and 13a,c inhibited the growth of cancer cells compared to Vinblastine. The structure–activity relationships were discussed.     

Synthetic utility of sydnones: synthesis of pyrazolines derivatized with 1,2,4-triazoles as antihyperglymic, antioxidant agents and their DNA cleavage study

Ring transformation of sydnone (1a–i) to 1,3,4-oxadiazoline-2-one (2a–i) was carried out using bromine in acetic anhydride. The compounds (2a–i) on heating with hydrazine hydrate gave 1,2,4-triazole (3a–i) in good yields. The structure of these unknown compounds was confirmed by IR, ¹H NMR, MS and elemental analysis. Further, these compounds were evaluated for the extent of penetration into biological membranes (clogP) drug likeliness and finally drug score was calculated. The title compounds were also screened for their antihyperglycemic, DNA cleavage and antioxidant activity.     

Synthesis of some new indolo[2,3-c]isoquinolinyl pyrazoles, -1,3,4-oxadiazoles and their biological activities

A new series of novel compounds [10-substituted 6H, 7H-indolo[2,3-c]isoquinolin-5-one-6-yl]carbohydrazides (3a–c), 1-[10-substituted 6H, 7H-indolo[2,3-c]isoquinolin-5-one-6-yl]fomyl-, -3′,5′-dimethylpyrazoles (4a–c), -3′,5′-diphenylpyrazoles (5a–c), -3′-methylpyrazol-5′-ones (6a–c) and -1′,3′,4′-oxidiazole-2′-thiones (7a–c) linked to indoloisoquinoline at position-6 through formyl bridge was prepared. The structures of these newly synthesized compounds were confirmed by their spectral studies and elemental analysis. These compounds have been screened for their antimicrobial and antioxidant activities. Compounds 4a, 4b, 5a, 5b, 5c, 6b, 7a, and 7c exhibited the maximum zone of inhibition against A. niger, A. flavus, and A. fumigatus. Compounds 4a, 5a, 5c, 6b, 6c, 7a, and 7b showed good antibacterial activity. Compounds 4b, 4c, 5b, 5c, 6a, 6b, 7a, 7b, and 7c showed good radical scavenging activity compared with standards.     

Synthesis, in vitro cytotoxicity, and antibacterial studies of new asymmetric bis-1,2,4-triazoles

A series of asymmetric bis-1,2,4-triazoles (4a–l) were synthesized from respective 1,2,4-triazole-3-thiocarbohydrazides (2a, b) via base catalyzed dehydrative cyclization of thiosemicarbazide intermediates (3a–l). The synthesized compounds were characterized by IR, ¹H-NMR, ¹³C-NMR, and Mass spectral studies. The asymmetric bis-1,2,4-triazole derivatives (4a–l) were evaluated for in vitro antioxidant activity by DPPH radical scavenging assay method. The compounds with significant antioxidant potential were evaluated for in vitro cytotoxicity by MTT assay method against HT29 (Human adenocarcinoma) and MDA-231 (Human breast cancer) cancer cell lines. All the synthesized compounds were evaluated for in vitro antibacterial activity against Bacillus subtilus (ATCC 6633), Staphylococcus aureus (ATCC-25923), Escherichia coli (ATCC-25922), and Pseudomonas aeruginosa (ATCC-27853).