Synthesis, characterization, and antimicrobial screening of some Mannich base sydnone derivatives

The title compounds (5a–j), (6a–j), and (7a–j) were prepared via a four-step procedure using starting material 4-methoxyaniline (1). The structure of all synthesized compounds was confirmed by FT-IR, ¹H NMR, ¹³C NMR, and CHN analysis. The synthesized compounds were tested for their antibacterial and antifungal activity (MIC) in vitro against organisms viz. B. subtilis, S. aureus, E. coli, P. aeruginosa, and C. albicans taking ciprofloxacin, ampicillin, streptomycin, penicillin-G, fluconazole, and nystatin as the standard drugs. Some of the compounds have shown significant 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.     

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.     

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, 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.     

Design, synthesis of some 2,6,9-trisubstituted purinyl thioureido derivatives and evaluation of antimicrobial activity

Some new trisubstituted purinyl thioureido were synthesized and evaluated for their in vitro antimicrobial activity against Gram positive and Gram negative strains and antifungal strain using a micro dilution procedure. Synthesized compounds 6a–j prove to be effective with minimum inhibitory concentration (MIC) (mg?ml^?1), among them 6a, 6d, and 6e showed excellent activity against a panel of microorganisms. The newly synthesized compounds were characterized using IR, ¹H-NMR, and elemental analysis.     

Anti-mycobacterial, cytotoxic activities of Knoevenagel and (E)-α,β-unsaturated esters and ketones from 2-chloronicotinaldehydes

Series of 2-chloronicotinaldehyde Knoevenagel derivatives 3a–r; (E)-α,β-unsaturated esters and ketones 5a–k were prepared and evaluated for their in vitro anti-mycobacterial activity against Mycobacterium tuberculosis H₃₇Rv (Mtb). Compounds 3e, 5b, 5d, 5e, 5g and 5i–k were shown potent to significant activity. Compound 5j is the most potent Mtb inhibitor (MIC: 4.89 μM) when compared to standard drugs Ethambutol (MIC: 7.63 μM) and Ciprofloxacin (MIC: 9.44 μM). Eight compounds displayed potent/significant activity against M. tuberculosis were chosen for the cytotoxicity against three cell lines (Raw 264.7, MCF7, and HeLa). Compound 5j displayed low toxicity with high selective index (15–30) and is an interesting new compound may serve for the development of therapeutics targeted against anti-mycobacterial compounds. This is the first report assigning in vitro anti-mycobacterial inhibitory activity and structure–activity relationship for this class of substituted 2-chloronicotinaldehyde derivatives and presents new family of compounds.     

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.     

Antimicrobial and anticancer effects of some 2-(substitutedsulfanyl)-N-(5-methyl-isoxazol-3-yl)acetamide derivatives

In the present study, some isoxazole-(benz)azole derivatives (3a–3j) were synthesized by considering antimicrobial and anticancer potencies of azole compounds. Chemical structures of obtained compounds (3a–3j) were confirmed by the data of spectral and elemental analyses. Anticancer activity evaluation was performed at two steps. Initially, cytotoxic effects of the compounds (3a–3j) on HT-29 (colon carcinoma) and C-6 (melanoma) cell lines were determined by MTT assay. Secondly, the compounds 3g–3i, which indicated significant cytotoxicity were selected and analysed for their inhibitory activity on DNA synthesis of carcinogenic cells. The compounds 3g and 3h showed notable DNA synthesis inhibition on both cancer cell lines. Antibacterial and antifungal activities of the synthesized compounds (3a–3j) were also examined. All of the compounds exhibited very poor antibacterial activity against gram negative and gram positive bacterial strains, whereas antifungal activity of the compounds 3a–3f was equal to that of Ketoconazole.     

Synthesis and biological evaluation of novel curcumin analogues as anti-inflammatory, anti-cancer and anti-oxidant agents

A series of novel curcumin analogues 5a–m were synthesized by Claisen-Schmidt condensation of various aromatic and heteroaromatic amides of 3-aminoactophenones 4a–m with 3-bromo-2,4,6-trimethoxybenzaldehyde and characterized by IR, ¹H NMR and mass spectroscopic analysis and were evaluated for anti-inflammatory, anti-cancer and anti-oxidant activity. Out of the 13 synthesized compounds, compounds 5f, 5j and 5m were excellent inhibitors of TNF-α and IL-6. Compounds 5c, 5e, 5b and 5d showed potent COX-2 inhibition, compounds 5d and 5f have shown good trypsin inhibition and compounds 5e, 5g and 5c exhibited excellent β-glucuronidase inhibition. Compounds 5l and 5m showed potent anti-cancer activity against selected five human cancer cell lines. All the compounds exhibited moderate free radical scavenging activity, while compounds 5a and 5m were excellent OH radical scavengers.     

Antibacterial and free radical scavenging potential of synthesized 7-hydroxy-2-aryl-6-aryldiazenyl-4H-chromen-4-ones

A series of 7-hydroxy-2-aryl-6-aryldiazenyl-4H-chromen-4-one derivatives (6a–m) was synthesized in quantitative yields and their structures were corroborated on the basis of FT-IR, ¹H, ¹³C NMR, ESI–MS, and elemental analysis data. The synthesized compounds were screened for in vitro antibacterial activities against a representative panel of Gram-positive and Gram-negative bacteria, as well as to evaluate their antioxidant potential using DPPH assay method. Bio-evaluation studies revealed that compounds 6c, 6d, 6e, 6j, and 6l exhibited moderate to good antibacterial activity against all the tested bacterial strains. Furthermore, from the antioxidant screening results, it has been observed that compounds 6c, 6e, and 6g manifested profound antioxidant potential (IC₅₀ <7.68 μM) in comparison to the standard antioxidant ascorbic acid.     

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, 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, 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 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.     

Synthesis and evaluation of 2,4,6-trisubstituted pyrimidine derivatives as novel antileishmanial agents

A series of new 2,4,6-trisubstituted pyrimidine derivatives 8(a–j) were synthesized by reacting substituted chalcones containing imidazole 6(a–d) and benzimidazole 7(a–f) with guanidine hydrochloride in the presence of strong base. Substituted chalcones were synthesized by reacting 4-(1H-imidazol-1-yl)benzaldehyde or 4-(1H-benzo[d]imidazol-1-yl)benzaldehyde with different substituted acetophenones in the presence of 40 % NaOH in methanol. The synthesized compounds were confirmed by IR, ¹HNMR, and mass spectral data and screened for antileishmanial activity. Antileishmanial activity was performed against Leishmania donovani parasite, and percentage lysis inhibition were calculated by meglumine antimoliate taking a positive control and chloroform (0.1 % CHCl₃) treatment served as control. Among all the compounds, 8h and 8j exhibited 50–57 % inhibition against promastigotes, thus providing new structural lead for antileishmanials.     

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 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 antimicrobial studies of a few novel thiazole derivatives

A series of novel N-[4-(substituted)-1,3-thiazol-2-yl]-2-(substituted)acetamide (9a–m) and methyl 2-(2-(2-(substituted)acetamido)thiazol-4-yl)acetate (9n–o) derivatives have been synthesized and compounds were characterised by spectral and analytical studies. All compounds were screened for their in vitro antibacterial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa and Klebsiella pneumonia by disc diffusion method and for antifungal activity against Penicillium marneffei, Trichophyton mentagrophytes, Aspergillus flavus and Aspergillus fumigatus by serial plate dilution method. Compounds 9b, 9e, 9m and 9o exhibited growth inhibition against all the tested bacterial strains, with MIC values varying from 12.5 to 6.25 μg/ml. Among the compounds tested for antifungal activity, 9a, 9b, 9d, 9j, 9k, 9p and 9n showed wide range of activity against all the tested strains. Most of the newly synthesized compounds were effective against fungal strains rather than bacterial strains. However, some of the compounds like 9a, 9e, 9j, 9k and 9i showed selective sensitivity against some of the bacterial strains whereas they were unable to sustain the growth of other strains.     

Zn(OTf)2-catalyzed three component, one-pot cyclocondensation reaction of some new octahydroquinazolinone derivatives and access their bio-potential

An efficient synthesis of some new octahydroquinazolinone derivatives 4a–x by the cyclocondensation reaction of corresponding 2-thi(oxo)-1,2-dihydroquinoline-3-carbaldehyde 1a–e, 1,3-dicarbonyl compounds 2a–b, and substituted urea 3a–c using zinc triflate as a catalyst in refluxing ethanol in high yield is described. The structures of new compounds have been characterized on the basis of elemental analysis, FT- IR, ¹H NMR, ¹³C NMR, and mass spectral data. All the synthesized compounds were evaluated for their antimicrobial activities against various microbes. Minimum inhibitory concentration values of all the 24 synthesized compounds were also determined. Some of the synthesized compounds exhibited excellent antimicrobial activity.