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 anticonvulsant activity of novel quinazolin-4(3H)-one derived pyrazole analogs

Eighteen novel 6,8-(dibromo/unsubstituted)-2-(methyl/phenyl)-3-(4-(5-(substitutedphenyl)-3-phenyl-4,5-dihydro-1H-pyrazole-1-carbonyl)phenyl)-quinazolin-4(3H)-ones 4a–4r were designed and synthesized in good yield. Antiepileptic screening of the title compounds was performed using MES and scPTZ seizures tests while the neurotoxicity was determined by rotorod test. In the preliminary screening, compounds 4d, 4e, 4p, 4q, and 4r were found active in MES model, while 4a, 4d, 4f, 4m, and 4p showed significant antiepileptic activity in scPTZ model. Further, all these eight compounds were administered to rats and compounds 4e, 4p, and 4q showed better activity than Phenytoin in oral route. Among these compounds 4p revealed protection in MES after i.p. administration at a dose of 30 mg/kg (0.5 h) and 100 mg/kg (4 h). The compound 4p also provided protection in the scPTZ at a dose of 100 mg/kg (0.5 h) and 300 mg/kg (4 h).     

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.     

A new neolignan and lignans from the stems of Lindera obtusiloba Blume and their anti-allergic inflammatory effects

A new neolignan, linderin A (1), together with six known lignans, (+)-xanthoxyol (2), pluviatilol (3), actiforin (4), (+)-syringaresinol (5), (+)-(7S,8R,8′R)-acuminatolide (6), and (+)-9′-O-trans-feruloyl-5,5′-dimethoxylariciresinol (7) were isolated from the stems of Lindera obtusiloba Blume (Lauraceae). Their chemical structures were elucidated by a combination of spectroscopic analysis and chemical reaction, and the absolute configuration of 1 was determined by Mosher’s esterification. The effect of compounds 1–7 on tumor necrosis factor (TNF)-α, interleukin(IL)-6, and their inhibitory activity of histamine release were examined using human mast cells. Among the lignans tested, compounds 1, 3, 4, 6, and 7 inhibited release of histamine from mast cells. Especially, compounds 1 and 4 suppressed the gene expressions of pro-inflammatory cytokines, TNF-α, and IL-6 in human mast cells. Our findings suggest that the lignan constituents in L. obtusiloba may contribute to its anti-allergic inflammatory effects.     

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 and characterization of novel benzo[d][1,3]dioxole gathered pyrazole derivatives and their antimicrobial evaluation

Benzo[d][1,3]dioxole gathered pyrazole derivatives (4a–i) were synthesized by the reaction of chalcones with phenyl hydrazine in presence of absolute alcohol as a solvent. Chalcones were prepared by the Claisen-Schmidt reaction between 1-(benzo[d][1,3]dioxol-5-yl)ethanone (2) and substituted aromatic aldehydes. The synthesized compounds were characterized by spectral and elemental analysis data. Furthermore, Benzo[d][1,3]dioxole gathered pyrazole derivatives (4a–i) were evaluated for their in vitro antimicrobial activity. Among the newly synthesized compounds 4a, 4c, 4 g and 4 h showed the excellent antifungal activity and as well as 4a and 4d showed the excellent antibacterial activity when compared to other compounds.     

Four new antioxidant phenylpropanoid glycosides from Microlepia pilosissima

Four new phenylpropanoid glycosides, 9-O-[β-D-glucopyranosyl-(1→2)-α-L-rhamnopyranosyl]-3,4-dimethoxy-cinnamic acid (1), 9-O-[β-D-glucopyranosyl-(1→2)-α-L-rhamnopyranosyl]-4-methoxycinnamic acid (2), 9-O-α-L-rhamnopyranosyl-3,4-dimethoxy-cinnamic acid (3), and 9-O-[6-Oacetyl-β-D-glucopyranosyl]-4-methoxy-cinnamic acid (4), together with three known compounds 9-O-α-L-rhamnopyranosyl-4-hydroxy-cinnamic acid (5), 9-O-β-D-glucopyranosyl-4-methoxycinnamic acid (6), and 9-O-β-D-glucopyranosyl-3,4-dimethoxy-cinnamic acid (7) were isolated from the 70% EtOH extract of the dry fronds of Microlepia pilosissima. Their chemical structures were elucidated by spectroscopic analysis. Moreover, 1 and 2 exhibited comparable scavenging activities with (±)-α-tocopherol against DPPH radicals, while compounds 3–7 displayed moderate antioxidant activities.     

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,antimicrobial, and cytotoxic activities of novel benzimidazole derivatives bearing cyanopyridine and 4-thiazolidinone motifs

A series of 6-(1H-benzo[d]imidazol-2-yl)-2-(2-(3-nitrophenyl)-4-oxothiazolidin-yl)-4-(aryl)nicotinonitriles 5a–l were synthesized and characterized by IR, ¹H NMR, ¹³C NMR, and mass spectrometry techniques. These novel compounds 5a–l were screened for their in vitro antimicrobial activity against different bacterial and fungal strains and in vitro cytotoxicity study (HeLa cell line) using MTT colorimetric assay. The results demonstrated that compounds 5c, 5e, and 5i–k exhibited excellent antibacterial activity, while compounds 5d, 5i, and 5k were found to be the most potent antifungal agents. From the standpoint of SAR studies, it was observed that the presence of electron donating groups remarkably enhanced the antimicrobial activity of newly synthesized compounds. Further, the results of preliminary MTT cytotoxicity studies on HeLa cells suggested that potent antimicrobial activity of 5c–e and 5i–k was accompanied by low cytotoxicity.     

Synthesis and antimicrobial activities of some isoxazolyl thiazolyl pyrazoles

A series of isoxazolyl thiazolyl pyrazoles 5a–d was synthesized by multi-step process, starting from 3-acetyl-4-hydroxy-6-methyl-2H-pyran-2-one (dehydroacetic acid, DHAA) 1. DHAA 1 was easily converted to thiosemicarbazone 2 which on reaction with α-bromoketones yielded thiazolyl hydrazones 3. Refluxing 3 in ethanol-acetic acid furnished 1-(5-hydroxy-3-methyl-1-substituted pyrazol-4-yl)-1,3-butanediones 4. Finally, the title compounds 5a–d were synthesized from 4 on treatment with hydroxylamine. The in vitro antimicrobial activity of compounds 3a–d, 4a–d and 5a–d were tested. Most of the synthesized compounds exhibited significant antibacterial and antifungal activities.     

Efficient synthesis of piperazine-2,6-dione and 4-(1H-indole-2-carbonyl)piperazine-2,6-dione derivatives and their evaluation for anticancer activity

Condensation of iminodiacetic acid 1 with various amines i.e., cyclohexanamine, 1-(3-aminopropyl)imidazole, pyridin-2-ylmethanamine, pyridin-3-ylmethanamine, pyridin-4-ylmethanamine, 2-morpholinoethanamine, thiophen-2-ylmethanamine, 2-(thiophen-2-yl)ethanamine, furan-2-ylmethanamine, 2-(pyrrolidin-1-yl)ethanamine, and 1-(3-aminopropyl) pyrrolidin-2-one 2a–k under microwave irradiation gave the corresponding piperazine-2,6-dione derivatives 3a–k in quantitative yields. Piperazine-2,6-dione derivatives 3a–k on condensation with 1H-indole-2-carboxylic acid under microwave irradiation gave the corresponding 4-(1H-indole-2-carbonyl)piperazine-2,6-dione derivatives 4a–k in quantitative yields. All the synthesized compounds (3a–k & 4a–k) were purified by crystallization and characterized by spectroscopic means. On screening at a concentration of 10 μM, compounds 3k, 4e, 4i breast (T47D), 4j lung (NCI H-522), 3i colon (HCT-15), 4e ovary (PA-1), and 4g liver (HepG-2) exhibited good anticancer activity.     

Synthesis, pharmacological activity evaluation and molecular modeling of new polynuclear heterocyclic compounds containing benzimidazole derivatives

Novel heterocyclic compounds containing benzimidazole derivatives were synthesized from 2-(1Hbenzimidazol-2-yl) acetonitrile (1) and arylhydrazononitrile derivative 2 was obtained via coupling of 1 with 4-methyl phenyldiazonium salt, which was then reacted with hydroxylamine hydrochloride to give amidooxime derivative 3. This product was cyclized into the corresponding oxadiazole derivative 4 upon reflux in acetic anhydride. Compound 4 was refluxed in DMF in the presence of triethylamine to give the corresponding 5-(1H-benzimidazol-2-yl)-2-p-tolyl-2H-1,2,3-triazol-4-amine 6. Treatment of compound 6 with ethyl chloroformate afforded 2,6-dihydro-2-(4-methylphenyl)-1,2,3-triazolo[4″,5″-4′,5′]pyrimido[1,6-a]benzimidazole-5(4H)-one (8). 1,2-bis(2-cyanomethyl-1H-benzimidazol-1-yl)ethane-1,2-dione (10) was synthesized via the condensation reaction of 2-(1H-benzimidazol-2-yl) acetonitrile (1) and diethyloxalate. The reactivity of compound 10 towards some diamine reagents was studied. The in vitro antimicrobial activity of the synthesized compounds was investigated against several pathogenic bacterial strains such as Escherichia coli O157, Salmonella typhimurium, E. coli O119, S. paratyphi, Pseudomonas aeruginosa, Staphylococcus aureus, Listeria monocytogenes and Bacillus cereus. The results of MIC revealed that compounds 12a–c showed the most effective antimicrobial activity against tested strains. On the other hand, compounds 12a, b exhibited high activity against rotavirus Wa strain while compounds 12b, c exhibited high activity against adenovirus type 7. In silico target prediction, docking and validation of the compounds 12a–c were performed. The dialkylglycine decarboxylase bacterial enzyme was predicted as a potential bacterial target receptor using pharmacophorebased correspondence with previous leads; giving the highest normalized scores and a high correlation docking score with mean inhibition concentrations. A novel binding mechanism was predicted after docking using the MOE software and its validation.     

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, anti-inflammatory, and cytotoxicity evaluation of 9,10-dihydroanthracene-9,10-α,β-succinimide and bis-succinimide derivatives

9,10-Dihydroanthracene-9,10-α,β-succinimide derivatives 4a–e and bis-succinimide derivatives 6a–e have been synthesized by grinding 9,10-dihydroanthracene-9,10-α,β-succinic anhydride 2 with various mono 3a–e and diamines 5a–e in quantitative yields. All the target compounds were fully characterized by spectrometric and spectroscopic means. Compounds 4a–e, 6a–e and recently reported compounds 4f–p were screened for anti-inflammatory and for cytotoxicity against five human cancer cell lines: T47D, NCI H-522, HCT-15, PA1, and HepG-2. Compounds 4e, 4i, 4j, and 4p exhibited good anti-inflammatory activity and compounds with interesting cytotoxic profile were 4c, 6e (T47D); 4e, 4o (NCI H-522); 4n (HCT-15); 4e, 4h, 4o (PA1); and 4a, 4e, 4f, 4i, 4o (HepG-2).     

Design, synthesis, anti-inflammatory, analgesic screening, and molecular docking of some novel 2-pyridyl (3H)-quinazolin-4-one derivatives

A novel series of 6-bromo-2-(4-pyridyl)-quinazolin-4(3H)-ones were synthesized by reacting 5-bromo anthranilic acid with isonictinoly chloride in the presence of acetic anhydride, which were further reacted with p-amino acetophenone to obtain 3-(4-acetylphenyl)-6-bromo-2-(pyridin-4-yl)quinazolin-4(3H)-one (3). Compound 3 underwent further reactions with different aldehydes to afford chalcone derivatives 4–10, which in turn underwent various cyclization reactions to afford cyclized products 15–18. 2-aminothiazole derivatives 12 obtained by reaction of 3 with bromine then with thiourea. Compound 14 obtained by treatment of 11 with KSCN followed by cyclization. Some of the synthesized compounds 4, 5, 12, 14, 15 and 18 were screened for both analgesic and anti-inflammatory activities. All tested compounds showed good analgesic and anti-inflammatory activity in comparison to the reference standard indomethacin. Compounds 4 and 5 showed the highest anti-inflammatory activity, while compounds 14 and 15 showed the highest analgesic activity among all the tested compounds.     

An efficient, solvent-free microwave-assisted synthesis and antimicrobial screening of 1,6-dihydropyrimidine analogues

A series of compounds 4-(4-(4-aminophenyl)-6-(aryl)-1,6-dihydropyrimidin-2-ylthio)butanenitriles 5a–l were synthesised by the reaction of allyl cyanide 4 with 3a–l. Compounds 3a–l were prepared from reaction between various chalcones 1a–l and thiourea in presence of catalytic amount of potassium hydroxide. Compounds 3a–l, and 5a–l were prepared by classical as well as MWI methods. Structures of the compounds were characterized by IR, ¹H NMR, ¹³C NMR and mass spectral data. The newly synthesized compounds 5a–l were screened for their antimicrobial activity against different strains of bacteria and fungi using serial broth dilution method. Compounds 5e, 5g and 5k were found to be most active with MIC of 25?μg/mL against selected bacterial strains, while compound 5d, 5f, 5j and 5k were found to be most active with MIC 50?μg/mL against selected fungal strains.     

New thiazolidine-2,4-diones as antimicrobial and cytotoxic agent

New (Z)-5-substituted-2,4-thiazolidinediones (3a–m) were easily prepared by the condensation of thiazolidine-2,4-dione (1) with suitable aldehydes (2a–m) via microwave irradiation technique. The reaction between (Z)-5-substituted-2,4-thiazolidinediones and 4-(bromomethyl) benzoic acid, using potassium carbonate as base in refluxing acetone, followed by a workup in acidic medium provided 4-(((Z)-5-substituted-2,4-dioxothiazolidin-3-yl)methyl) benzoic acid derivatives (4a–m). The structures of the newly synthesized compounds were confirmed by IR, ¹H NMR, ¹³C NMR spectral studies, and elemental analysis. All compounds were evaluated for their in vitro antimicrobial and cytotoxic activities. Antibacterial and antifungal results revealed that most of the compounds showed significant activity where as compounds 4c and 4g are found to be broad spectrum antibacterial and antifungal properties, the MIC values were observed in the range of 2–4 and 2–8?μg/ml, respectively. In MTT cytotoxicity studies, the compound 4g was found most potent. In HeLa, HT29, A549, and MCF-7 cells, the IC₅₀ values were observed in the range of 30–36?μM.     

Synthesis of 1-(4-aminosulfonylphenyl)-3,5-diarylpyrazoline derivatives as potent antiinflammatory and antimicrobial agents

A new series of 1-(4-aminosulfonylphenyl)-3,5-diaryl pyrazolines (5) was synthesized by the reaction of appropriate chalcones 3 with 4-hydrazinobenzenesulfonamide hydrochloride (4) in ethanol in the presence of catalytic amount of acetic acid. All newly synthesized compounds were in vivo evaluated for their antiinflammatory activity using carrageenan-induced rat paw edema assay. Five of the newly synthesized compounds, 5d, 5g, 5h, 5i, and 5m displayed significant antiinflammatory activity, greater than 55% inhibition 3?h after the carrageenan injection. All the newly synthesized compounds were evaluated for their in vitro antimicrobial activity against two Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis); two Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), and two yeast (Candida albicans and Saccharomyces cerevisiae). Some of the newly synthesized compounds 5a, 5f, 5g, 5h, 5j, and 5k showed excellent antifungal activity, greater than the reference drug amphotericin B, against Saccharomyces cerevisiae.     

Synthesis, characterization and antimicrobial screening of hybrid molecules containing benzimidazole-pyrazole and pyridine nucleus

The rising prevalence of multi-drug resistant Gram-positive, Gram-negative bacteria and fungi continues to provide momentum for search and development of novel active antimicrobial agents against these pathogens. In continuation to this, the present article deals with the synthesis and antimicrobial activity of a novel series of (3-(1H-benzo[d]imidazol-2-yl)-5-(aryl)-4,5-dihydro-1H-pyrazol-1-yl)(pyridin-4-yl)methanones 4a–n, synthesized by the reaction of benzimidazolyl chalcones with isoniazide 3. The structures of synthesized compounds were elucidated on the basis of IR, NMR, and mass spectra. The newly synthesized compounds 4a–n were screened for their antimicrobial activity against different strains of bacteria and fungi using serial broth dilution method. Compounds 4d, 4f, 4h, and 4g were found to be most active with MIC of 25?μg/mL against selected bacterial strains. Compounds 4c, 4g, and 4n were found to be most active with MIC of 100?μg/mL against selected fungal strains.     

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.