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, antimicrobial and antioxidant activities of some new indole derivatives containing pyridopyrimidine and pyrazolopyridine moieties

New indole analogues containing pyrido[2,3-d]pyrimidin-4-(3H)-ones (3a–i), pyrazolo[3,4-b]pyridin-3-amines (4a–i) and pyrido[2,3-d]pyrimidin-4-amines (5a–i) were synthesized using appropriate synthetic routes. These newly synthesized compounds were screened for their antimicrobial and antioxidant activities. Compounds 3a, 3g, 4c, 4h, 4i, 5a, 5c and 5f exhibited good antibacterial and antifungal activities. The compounds 3b, 3c, 3g, 4a, 4h, 4i and 5a exhibited good radical scavenging activity. Compounds 3a and 4d exhibited good metal chelating activity compare with standards.     

Design and evaluation of new hybrid pharmacophore quinazolino-tetrazoles as anticonvulsant strategy

The anticonvulsant study of 25 newly synthesized quinazolin-4(3H)-one substituted 1H and 2H-tetrazoles (6a–6d, 7a–7b, 8a–8i, 8a′–8i′) was executed. The study employing the maximal electroshock and subcutaneous pentylenetetrazole (scPTZ) screens, the ‘gold standards’ in the preliminary anticonvulsant breakthrough and the neurotoxicity study applying the rotorod test unveiled a triad of compounds 6c, 7b and 8i′ as the looms amongst the compendium of synthesized compounds. The quantification data of these compounds following oral administration in rats showcased 7b to endorse a remarkable position in the MES screen with a protective indice (PI) of >39.67 and 6c in the scPTZ delineating a PI > 3.10, respectively. All the potent compounds were destitute of toxicity.     

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 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,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, antitumor activity of 2-amino-4H-benzo[h]chromene derivatives, and structure–activity relationships of the 3- and 4-positions

Several 2-amino-4H-benzo[h]chromenes (3a–i) and (5a–h) were obtained by reaction of 4-chloro-1-naphthol (1) with α-cyanocinnamonitrile (2a–i) or ethyl α-cyanocinnamate derivatives (4a–h), respectively. 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, Colchicine, and Doxorubicin well-known anticancer drugs, using MTT colorimetric assay. Among them, the compounds 5e, 3c, 5f, b, d, 3d, 5c, a were the most active against MCF-7, 5a against HCT-116 and 5a, 3e, a against HepG-2 as compared with the standard drug Vinblastine, while the compounds 5e, 3c, 5f, b, d, 3d, 5c, a, h, 3i, g, a, e were the most active against MCF-7, 5a, c, e, f, b, 3e, c, g, b, 5d, h, 3d, i, 5g against HCT-116, 5a, 3e, a, 5e, 3c, 5d, c, f, 3b, 5g, 3g, 5h against HepG-2 as compared with the standard drug Colchicine. The structure–activity relationships of the 3- and 4-positions were discussed.     

Synthesis, antimicrobial, and antioxidant activities of some new indole analogues containing pyrimidine and fused pyrimidine systems

To examine new leads with potential antimicrobial and antioxidant activities, a new series of tetrahydropyrimidines (2a–c, 3a–c and 4a–c), pyrazolo[3,4-d]pyrimidines (5a–c), and ditetrazolo[1,5-a;1′,5′-c]pyrimidines (6a–c) were synthesized in this study using appropriate synthetic routes. The newly synthesized compounds have been tested for their antimicrobial and antioxidant activities against DPPH stable free radical. In the case of antibacterial activity, compounds 2a, 6a, and 6c exhibited the maximum zone of inhibition against Staphylococcus aureus; compound 6c exhibited maximum zone of inhibition against Pseudomonas aeruginosa; and compound 2a showed maximum inhibitory growth against Klebsiella pneumonia. While in the case of antifungal activities, compound 5a showed good zone of inhibition against Aspergillus oryzae, compounds 2b and 6a exhibited maximum zone of inhibition against Aspergillus niger. In case of antioxidant activities, compound 2a showed the highest DPPH radical scavenging activity.     

Synthesis and antimicrobial activity of 5-chloroindoline-2,3-dione derivatives

A series of 3-(5-chloro-2-oxoindolin-3-ylideneamino)-2-arylthiazolidin-4-ones 4a–k and 5-chloro-3-(3-chloro-2-oxo-4-arylazetidin-1-ylimino)indolin-2-ones 5a–k was synthesized. The structures of final compounds were confirmed by analytical (C, H, N) and spectral (FT-IR, ¹H NMR, ¹³C NMR and Mass) data. The synthesized compounds were screened for possible antibacterial and antifungal activity. Compounds 4c, 4f, 4g, 4h, 4i, 4j, 5c, 5f, 5g, 5h, 5i and 5j showed substantially significant activity.     

Synthesis, characterization, and in vitro antimicrobial evaluation of new 5-chloro-8-bromo-3-aryl-1,2,4-triazolo[4,3-c]pyrimidines

A series of new 5-chloro-8-bromo-3-aryl-1,2,4-triazolo[4,3-c]pyrimidines (4a–j) have been accomplished in excellent yields by the oxidative cyclization of pyrimidinylhydrazines (3a–j) of various aryl aldehydes with one equivalents of iodobenzene diacetate in methanol. The chemical structures of the synthesized compounds were confirmed by elemental analyses, FT-IR, ¹H NMR, ¹³C NMR, and mass spectral studies. Ten new compounds (4a–j) were tested in vitro for their antimicrobial activity against clinically isolated strains. Variable and modest activities were observed against the investigated strains of bacteria and fungi. Compounds 4f, 4i, and 4j demonstrated good antimicrobial activity against all the tested microbial strains.     

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.     

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, 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).     

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 and pharmacological evaluation of novel thienopyrimidine and triazolothienopyrimidine derivatives

Novel tricyclic thienopyrimidines (2, 3, 5, 8) and triazole-fused tetracyclic thienopyrimidines (6a–c and 9a–c) were synthesized from the precursor 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carbonitrile (1). The structures of newly synthesized compounds were established by spectral and analytical data. The title compounds were screened for analgesic, anti-inflammatory, ulcerogenicity index, and antibacterial activities. Test compounds exhibited significant activity, the compounds (6a–c) and (9a–c) showed more potent analgesic activity, and the compounds (6c) and (9c) showed more potent anti-inflammatory activity than the reference standard Diclofenac Sodium. All the synthesized compounds exhibited remarkable antibacterial activity.     

Design, characterization, computational studies, and pharmacological evaluation of substituted-N′-[(1E) substituted-phenylmethylidene]benzohydrazide analogs

A series of substituted-N′-[(1E)-substituted-phenylmethylidene]benzohydrazide analogs were synthesized and authenticated by TLC, UV–Visible, FTIR, and NMR spectroscopic techniques. The physicochemical similarity of the new analogs with standard drugs was assessed by calculating from a set of ten physicochemical properties using software programs. The information so obtained can be related to prediction of biological activity for important targets. All the target compounds 4a–n were evaluated for their antioxidant, anti-inflammatory, and antimicrobial activity using different in vitro models. The test compounds demonstrated good similarity values with respect to the standard drugs. The compounds 4c, 4d, and 4e have emerged as important lead compounds showing potential anti-inflammatory; and 4b, 4f, and 4c having antioxidant profile. While studying MIC against bacterial strains 4c, 4f, 4i, 4k, and 4m were most active among all the target compounds. All compounds were found to have very good antifungal activity. The compounds having nitro substitution at the arylidene moiety i.e., 4c and 4f showed the most potent antifungal as well as antibacterial activities. While studying total antioxidant activity, all target compounds were found to have good antioxidant activity.     

Synthesis, biological evaluation, and molecular modeling studies of novel heterocyclic compounds as anti-proliferative agents

Two novel series of heterocyclic compounds have been synthesized. In first series, isatin was allowed to react with substituted aromatic/cyclic carbonyl compounds to get desired mannich bases (2a–e). In second series, 4,5-disubstituted oxazoles (6a–p) were synthesized. Eight compounds (2c, 6a, 6e, 6f, 6i, 6j, 6m, and 6n) were screened for anticancer activity in 60 cell lines. Compound 2c, 1-[(4,7,7-trimethyl-3-oxobicyclo[2.2.1]heptan-2-yl)methyl]indoline-2,3-dione, showed maximum activity and thus, selected for further evaluation at five dose level screening. Furthermore, molecular docking studies of compounds 2c into the colchicine-binding site of tubulin, revealed possible mode of inhibition by the compound.     

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, 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.     

Synthesis and biological evaluation of novel 4,5-dihydropyrazole derivatives as potent anticancer and antimicrobial agents

A focused library of 4,5-dihydropyrazole dervivatives (4, 5, 6, 7a–h, 8, 9a–g, and 10a–g) were synthesized from novel 5-(2,6-difluorophenyl)-3-phenyl-4,5-dihydropyrazole-1-carbothioamide 4. The synthesized compounds were characterized using elemental analysis and spectral data (IR, mass spectra, ¹H and ¹³C NMR) and evaluated for antimicrobial activity by broth dilution method and in vitro anticancer activity. Among the synthesized compounds 7a, 9c, 9g, and 10d exhibit broad spectrum antimicrobial activity against tested microbial strains. The in vitro cancer results ascertain 7a, 9c, and 10d are most potent molecules in comparison to reference standard cisplatin.