Synthesis and antimicrobial activity of some 7‐aryl‐5,6‐dihydro‐14‐aza[1]benzopyrano[3,4‐b]phenanthren‐8H‐ones

The title compounds, 7‐aryl‐5,6‐dihydro‐14‐aza[1]benzopyrano[3,4‐b]phenanthren‐8H‐ones 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h , 3i , 3j , 3k , 3l have been synthesized by reacting various 4‐hydroxy coumarins 1a , 1b , 1c with 2‐arylidene‐1‐tetralones 2a , 2b , 2c , 2d in the presence of ammonium acetate and acetic acid under Krohnke's reaction condition. The structures of all the synthesized compounds were supported by analytical, IR, ¹H‐NMR, and ¹³C‐NMR data. All the synthesized compounds 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h , 3i , 3j , 3k , 3l have been screened for their antibacterial activities against Escherichia coli (Gram ?ve bacteria), Bacillus subtilis (Gram +ve bacteria), and antifungal activity against Candida albicans (Fungi). J. Heterocyclic Chem., (2011).     

Efficient Synthesis of Novel 3‐Phenyl‐5‐thioxo‐3,4,5,6‐tetrahydroimidazo[4,5‐c]pyrazole‐2(1H)‐carbothioamide Derivatives Using a CeO2–MgO Catalyst and Evaluation of Antimicrobial Activity

Imidazo[4,5‐c ]pyrazole derivatives ( 3a–f , 4a–f , and 5a–f ) were efficiently synthesized by one‐pot three‐component reactions using CeO₂–MgO as the catalyst. The synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, and mass spectroscopic analyses. The in vitro antimicrobial activity of the synthesized compounds against various bacterial and fungal strains was screened. Compound 3b was highly active [minimum inhibitory concentration (MIC): 0.5 μg/mL] against Gram‐positive Staphylococcus aureus , and compounds 3b , 3f , 4d , and 4e were highly active (MIC: 0.5, 2, 2, and 0.5 μg/mL, respectively) against Gram‐negative Pseudomonas aeruginosa and Klebsiella pneumoniae , relative to standard ciprofloxacin in the antibacterial activity screening. Compounds 3b and 4f were highly active (MIC: 4 and 0.5 μg/mL, respectively) against Aspergillus fumigatus and Microsporum audouinii in the antifungal activity screening compared with the clotrimazole standard.     

Synthesis and Antimicrobial Evaluation of Some New 4,5′‐Bisthiazoles

Thiazole and bisthiazole derivatives represent a prevalent scaffold in the antimicrobial drug discovery. Therefore, we have decided to synthesize some new series of 4,5′‐bisthiazoles. A total of 17 compounds were synthesized, their structural elucidation being based on elemental analysis (C,H,N,S) and spectroscopic data (MS and ¹H NMR). Their in vitro antimicrobial activities were assessed against several Gram‐positive and Gram‐negative bacteria strains and also against one fungal strain (Candida albicans) using the difusimetric method. Some of the compounds showed modest to good antibacterial activity against Gram‐negative Escherichia coli and Salmonella typhimurium and Gram‐positive Staphylococcus aureus and Bacillus cereus bacterial strains. All of the synthesized compounds showed moderate to very good antifungal activity against C. albicans.     

New thiazolidine‐2,4‐dione derivatives combined with organometallic ferrocene: Synthesis,structure and antiparasitic activity

Favourable physicochemical properties of an organometallic ferrocene and antiplasmodial potency of compounds containing the thiazolidine‐2,4‐dione framework (TZD‐4) prompted us to explore compounds containing both the thiazolidine‐2,4‐dione core and the ferrocenyl unit with the primary aim of identifying compounds with promising antiprotozoal activities. Thus, a new series of rationally designed ferrocene‐based thiazolidine‐2,4‐dione derivatives, containing a selection of secondary cyclic amines, was synthesised and fully characterised using standard spectroscopic techniques. The resulting compounds were screened for their antiplasmodial and antitrypanosomal activities against both the chloroquine‐resistant (Dd2) strain of Plasmodium falciparum and the Nagana Trypanosoma brucei brucei 427. The general trend that emerged indicated that the target compounds were more selective towards T. b. brucei compared to the P. falciparum parasite. Moreover, the analogues bearing methylpiperazine ( 8a ) and piperidine ( 8b ) rings were more active against T. b. brucei compared to hit compound TZD‐4. Except compound 8b , which appeared promising, none of the synthesised compounds showed better activity than TZD‐4 against the P. falciparum parasite. All the synthesised compounds were non‐toxic and often showed >90% viability of the HeLa cell line screened.     

Synthesis and antimicrobial activity of novel 2‐(aryl)‐3‐[5‐(2‐oxo‐2H‐3‐chromenyl)‐1,3‐oxazol‐2‐yl]‐1,3‐thiazolan‐4‐ones

A series of novel 2‐(aryl)‐3‐[5‐(2‐oxo‐2H‐3‐chromenyl)‐1,3‐oxazol‐2‐yl]‐1,3‐thiazolan‐4‐ones 4a , 4b , 4c , 4e , 4f , 4g , 4h , 4i , 4j have been synthesized and assayed for their antibacterial activity against Gram‐positive bacteria viz. Bacillus subtilis (ATCC 6633), Staphylococcus aureus (ATCC 6538p), Micrococcus luteus (IFC 12708), and Gram‐negative bacteria viz. Proteus vulgaris (ATCC 3851), Salmonella typhimurium (ATCC 14028), Escherichia coli (ATCC 25922), and also antifungal activity against Candida albicans (ATCC 10231), Aspergillus fumigatus (HIC 6094), Trichophyton rubrum (IFO 9185), and Trichophyton mentagrophytes (IFO 40996). Among the screened compounds, 4d , 4e , 4f , 4g , and 4j exhibited potent inhibitory activity compared with the standard drug at the tested concentrations. The results reveal that, the presence of difluorophenyl in 4f and pipernyl ring in 4j at 2‐position of thiazolidine‐4‐one ring show significant inhibitory activity. The other compounds also showed appreciable activity against the test bacteria and fungi and emerged as potential molecules for further development. J. Heterocyclic Chem., 2011.     

Design,synthesis of (Z)‐3‐benzyl‐5‐((1‐phenyl‐3‐(3‐((1‐ substituted phenyl‐1H‐1,2,3‐triazol‐4‐yl)methoxy)phenyl)‐1H‐pyrazol‐4‐yl)methylene)thiazolidine‐2,4‐dione analogues as potential cytotoxic agents

In an attempt to achieve promising cytotoxic agents, a series of new (Z)‐3‐benzyl‐5‐((1‐phenyl‐3‐(3‐((1‐substituted phenyl‐1H‐1,2,3‐triazol‐4‐yl)methoxy)phenyl)‐1H‐pyrazol‐4‐yl)methylene)thiazolidine‐2,4‐diones 10 a‐n were designed, synthesized, and characterized by ¹H NMR, ¹³C NMR, IR, and ESI‐MS techniques. These compounds synthesized from appropriate reaction procedures with better yields. All the novel synthesized compounds 10a‐n were evaluated for their cytotoxic activity against the MCF‐7 cell line (Human breast cancer cell line) at different concentrations of 0.625, 1.25, 2.5, 5, and 10 μM, respectively. The cytotoxic evaluation assay is presented in terms of IC₅₀ values and percentage cell viability reduction compared against standard drug cisplatin. Among all novel synthesized compounds 10a‐n , some of the representative analogues particularly 10g and 10e exhibit remarkable cytotoxic activity with IC₅₀ values 0.454 and 0.586 μM, comparable to that of the standard drug cisplatin, and some analogues 10d , 10f , 10k, and 10m also have shown significant activity.     

Synthesis and Antimicrobial Activity of Some Novel [4‐(1,2,3‐thiadiazol‐4‐yl)phenoxy]methylene anchored 1,3,4‐triazoles and 1,3,4‐thiadiazoles

A series of novel [4‐(1,2,3‐thiadiazol‐4‐yl)phenoxy]methylene anchored 1,3,4‐triazoles ( 8a , 8b , 8c , 8d , 8e , 8f , 8g , 8h ) and 1,3,4‐thiadiazoles ( 9a , 9b , 9c , 9d , 9e , 9f , 9g , 9h , 9i ) were synthesized from thiosemicarbazide ( 7a , 7b , 7c , 7d , 7e , 7f , 7g , 7h , 7i , 7j ). The structures of these newly synthesized compounds were confirmed on the basis of IR, ¹H‐NMR, mass spectral techniques, and elemental analysis. The in vitro antimicrobial screenings of the synthesized compounds were carried out against four bacterial pathogens, namely Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa and three fungal pathogens Candida albicans, Aspergillus niger and Aspergillus clavatus, using broth microdilution minimum inhibitory concentration method. The compounds 7d , 7j , 8a , 9a , 9b , and 9i exhibited promising antibacterial activity against the tested strains, whereas some compounds were found to be active against one of the tested bacterial strains.     

Synthesis of 1,3‐thiazole and 1,2,4‐oxadiazole substituted spiro[3H‐indole‐3,2′‐thiazolidine]‐2,4′(1H)‐diones

Some new derivatives of spiro[3H‐indole‐3,2′‐thiazolidine]‐2,4′(1H)‐dione with the heterocyclic ring such as substituted thiazole and 1,2,4‐oxadiazole attached to the indolinone ring via CH₂ linkage has been synthesized in moderate yields. The synthesis have been carried out by making use of the reactivity of the NH group of the indolinone moiety present in spiro[3H‐indole‐3,2′‐thiazolidine]‐2,4′(1H)‐dione.     

Synthesis and Evaluation of Novel 5‐cyclohexyl‐2‐(4″‐substitutedphenyl)‐3‐(2″‐substitutedphenyl)4H‐2,3,3a,5,6,6a‐hexahydropyrrolo[3,4‐d]isoxazole‐4,6‐dione Derivatives for Their In Vitro Antioxidant and Antibacterial Activities

1,3‐Dipolar cycloaddition reactions of N‐cyclohexyl maleimide ( 1 ) with azomethine N‐oxide ( 2 ) have afforded novel isoxazolidine ( 3 ) in excellent yield. Their structures have been characterized from their IR, ¹H‐NMR, ¹³C‐NMR, ¹H,¹H‐COSY, MS(ESI), and elemental analysis techniques. In vitro antibacterial activity of the synthesized compounds were investigated against a representative panel of pathogenic strains specifically two Gram‐positive bacteria (Staphylococcus aureus and Streptococcus pyogenes ) and two Gram‐negative bacteria (Pseudomonas aeruginosa and Escherichia coli ) using agar‐well diffusion assay. Some of the compounds ( 3a , 3k , 3n , and 3o ) exhibited promising antibacterial activities. All the synthesized compounds have also been screened for their antioxidant activities and were found to be significantly active.     

Synthesis,Structure, and Biological Activities of 10‐Substituted 3,3,6,6‐Tetramethyl‐9‐Aryl‐3,4, 6,7,9,10‐hexahydroacridine‐1,8(2H,5H)‐dione Derivatives

A series of 10‐substituted‐3,3,6,6‐tetramethyl‐9‐aryl‐3,4,6,7,9,10‐hexahydroacridine‐1,8(2H ,5 H )‐dione derivatives 2 were synthesized by reaction of compounds 1 with amines. The compounds 1 were effectively prepared by 5,5‐dimethylcyclohexane‐1,3‐dione and aldehydes in the presence of a little amount of L‐proline as catalyst at room temperature. All the compounds were characterized by IR, MS, and ¹H NMR. The crystal data of 1b and 2d were collected by X‐ray single‐crystal diffraction, and compounds 2b and 2d exhibited better inhibitory activity against HepG2 cells.     

Synthesis of New 2,4‐Diaryl‐6‐methyl‐5‐nitropyrimidines as Antibacterial and Antioxidant Agents

A new series of 2,4‐diaryl‐6‐methyl‐5‐nitropyrimidines ( 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i ) were synthesized in good yields by Suzuki–Miyaura coupling of 2,4‐dichloro‐6‐methyl‐5‐nitropyrimidine ( 3 ) with various aryl boronic esters ( 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i ) in the presence of 1,1′‐ bis(diphenylphosphino)ferrocene dichloropalladium(II) (Pd(dppf)₂Cl₂). Further, antibacterial and antioxidant properties were screened for the title compounds 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i . Most of the compounds possessed significant activity against Gram‐positive bacteria Staphylococcus aureus and Bacillus subtilis and Gram‐negative bacteria Escherichia coli and Klebsiella pneumoniae. The antioxidant activity of the title compounds showed significant antioxidant activity when compared with vitamin C.     

Synthesis of New Gluco‐, Galacto‐, and Mannopyranosylthiazoles,Thiazolidinones, and Pyranosylthiazlidin‐4‐ones from Sugar Thiosemicarbazone Derivatives

A new series of potentially biological active derivatives, namely alkyl‐2‐((4‐oxo‐2‐(phenylimino)‐3‐(β‐d ‐pyranosyl‐2‐ylamino)thiazolidine‐5‐ylidene)acetate ( 5a–f ), 4‐(4‐bromophenyl)thiazol‐2(3H)‐ylidene)hydrazinyl)‐β‐d ‐pyranosyl ( 4a–c ), and 5‐(4‐bromophenyl)‐2‐(phenylimino)‐3‐(β‐d ‐pyranosyl‐2‐ylamino)thiazolidine‐4‐one ( 6 ) were synthesized via a reaction of the sugar thiosemicarbazone derivatives with 2,4′‐dibromoacetophenone, dialkylacetylenedicarboxylate, and ethylbromoacetate, respectively. The structures of the synthesized compounds were established by spectroscopic methods (FT‐IR, ¹H NMR, ¹³C NMR, and 2D NMR) and elemental analyses. Furthermore, the effect of various solvents at reflux and also ambient temperature on the reactions of the sugar thiosemicarbazone with 2,4′dibromoacetophenone, diethyl acetylenedicarboxylate, and dimethyl acetylenedicarboxylate was investigated. © 2013 Wiley Periodicals, Inc. Heteroatom Chem 24:200–207, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.21083     

Microwave induced synthesis of the thiazolidine‐2,4‐dione motif and the efficient solvent free‐solid phase parallel syntheses of 5‐benzylidene‐thiazolidine‐2,4‐dione and 5‐benzylidene‐2‐thioxo‐thiazolidine‐4‐one compounds

Novel microwave induced method for the synthesis of thiazolidine‐2,4‐dione motif under solvent phase conditions is developed. Further we report an efficient, microwave assisted method for the parallel syntheses of biologically important 5‐benzylidene‐thiazolidine‐2,4‐dione and 5‐benzylidene‐2‐thioxothiazolidine‐4‐one compounds under solid‐phase and solvent‐free conditions. A comparative study between the developed microwave methods and the conventional methods is described. We have also illustrated the possible mechanism behind to address the reason why piperidine, acetic acid and silica gel enhanced the Knoevenagel condensation reaction.     

New synthesis and reactivity of 3‐bromoacetyl‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one with binucleophilic amines

3‐(Bromoacetyl)‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one was synthesized by the reaction of dehydroacetic acid (DHAA) with bromine in glacial acetic acid. Novel heterocyclic products were synthesized from the reaction of bromo‐DHAA with alkanediamines, phenylhydrazines, ortho‐phenylenediamines, and ortho‐aminobenzenethiol. The obtained new products 3‐(2‐N‐substituted‐acetyl)‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐ones, 4‐hydroxy‐3‐[1‐hydroxy‐2‐(2‐phenylhydrazinyl)vinyl]‐6‐methyl‐2H‐pyran‐2‐one, 1‐(2,4‐dinitrophenyl)‐7‐methyl‐2,3‐dihydro‐1H‐pyrano[4,3‐c]pyridazine‐4,5‐dione, 3‐(3,4‐dihydroquinoxalin‐2‐yl)‐4‐hydroxy‐6‐methyl‐2H‐pyran‐2‐one/3‐(3,4‐dihydroquinoxalin‐2‐yl)‐6‐methyl‐2H‐pyran‐2,4(3H)‐dione, 6‐methyl‐3‐(3,4‐dihydroquinoxalin‐2‐yl)‐2H‐pyran‐2,4(3H)‐dione, and (E)‐3‐(2H‐benzo[b][1,4]thiazin‐3(4H)‐ylidene)‐6‐methyl‐2H‐pyran‐2,4(3H)‐dione were fully characterized by IR, ¹H and ¹³C NMR, and mass spectra. J. Heterocyclic Chem., 2011.     

Synthesis and Antimicrobial Activity of N‐[(2Z)‐3‐(4,6‐Substitutedpyrimidin‐2‐yl)‐4‐phenyl‐1,3‐thiazol‐2(3H)‐ylidene]‐3, 5‐dinitrobenzamide Analogues

In this study, we have synthesized 1‐(4,6‐disubstitutedpyrimidin‐2‐yl)‐3‐(3,5‐dinitrobenzoyl)‐thiourea derivatives ( 1a , 1b , 1c , 1d , 1e , 1f , 1g , 1h ) and N‐[(2Z)‐3‐(4,6‐disubstitutedpyrimidin‐2‐yl)‐4‐phenyl‐1,3‐thiazol‐2(3H)‐ylidene]‐3, 5‐dinitrobenzamide ( 2a‐2h ) analogues and characterized by IR spectroscopy, NMR spectroscopy, elemental analysis, and single crystal X‐ray diffraction data. The compounds ( 2a‐2h ) were screened for antimicrobial activity against Gram positive, Gram negative, and fungal species. The results of antimicrobial study indicated that compounds showed most potential and appreciable antibacterial and antifungal activities.     

Synthesis and Antifungal Activity of Novel Furan‐2,4‐dione Derivatives Containing Substituted Phenylhydrazine Moiety

A series of novel 3‐(2‐(substituted phenyl)hydrazinylmethylidene)furan‐2,4(3H,5H)‐diones were designed and synthesized with ethyl 4‐chloroacetoacetate as the starting material. Their structures were confirmed by FT‐IR, ¹H NMR, ¹³C NMR, EI‐MS and elemental analysis. Bioassay data demonstrated that these compounds exhibited remarkable antifungal activity against Fusarium graminearum, Botrytis cinerea, Rhizoctonia cerealis and Colletotrichum capsici. Compound 3‐(2‐(4‐bromophenyl)hydrazinylmethylidene)furan‐2,4(3H,5H)‐dione ( 5g ) had excellent bioactivity against Botrytis cinerea with an EC₅₀ value of 0.18 μg/mL ‐ markedly lower than the 0.24 μg/mL of the commercial fungicide procymidone. The result revealed that introducing the halogenated phenylhydrazine at the 3‐position of furan‐2,4(3H, 5H)‐dione was an effective way to design new tetronic acid derivatives as new fungicides.     

Synthesis of chloro,fluoro, and nitro derivatives of 7‐amino‐5‐aryl‐6‐cyano‐5H‐pyrano pyrimidin‐2,4‐diones using organic catalysts and their antimicrobial and anticancer activities

Chloro, fluoro, and nitro derivatives of 7‐amino‐5‐aryl‐6‐cyano‐5H‐pyrano pyrimidin‐2,4‐diones were produced by reacting malononitrile, barbituric acid, and aromatic aldehydes together with a DABCO catalyst in an aqueous one‐pot reaction. This is the first report of these compounds being synthesized with DABCO as a catalyst, which produced the compounds in yields in excess of 90%. The 2,4‐difluoro derivative ( 11 ) was novel. The structures of the synthesized compounds were elucidated by means of ¹H, ¹³C, and 2D NMR spectroscopy. Compound 2 (2‐Cl derivative) had MBC values of <200μM against both Staphylococcus aureus and MRSA, and the 2‐nitro derivative 5 had an MBC of 191μM against the Gram–ve Escherichia coli. The synthesized compounds were also tested for their anticancer activity against a HeLa cell line, where all the compounds showed better activity (IC₅₀ values between 129μM and 340μM) than 5‐fluorouracil, a commonly known anticancer drug.     

A “One Pot,” Environmentally Friendly,Multicomponent Synthesis of 2‐Amino‐5‐cyano‐4‐[(2‐aryl)‐1H‐indol‐3‐yl]‐6‐hydroxypyrimidines and Their Antimicrobial Activity

A series of multifunctional 2‐amino‐5‐cyano‐4‐[(2‐aryl)‐1H‐indol‐3‐yl]‐6‐hydroxypyrimidines ( 4a , 4b , 4c , 4d , 4e , 4f ) was synthesized by multicomponent reaction of 3‐formylindole ( 1 ), cyanoethylacetate ( 2 ), and guanidine hydrochloride ( 3 ) with NaOH by using green chemical techniques, viz. microwave irradiation and grindstone technology. The same reactants when refluxed in ethanol also gave titled compounds ( 4a , 4b , 4c , 4d , 4e , 4f ). Compared with conventional procedure, the reaction can be carried out under milder conditions, requiring a shorter reaction time and giving higher yields following the green chemistry methodology. All the synthesized compounds have been characterized on the basis of elemental analyses and spectral data (IR, ¹H NMR, ¹³C NMR, and mass). All synthesized compounds were also evaluated for their antimicrobial activity against nine pathogenic bacteria, antifungal activity against Rhizopus stolonifer, Aspergillus flavus, and Fusarium oxysporum and antibacterial activity against Escherichia coli and Pseudomonas aeruginosa at different concentrations. Most of the compounds showed mild to moderate activity.     

Synthesis,Antimicrobial, and Antioxidant Screening of Aryl Acetic Acid Incorporated 1,2,4‐Triazolo‐1,3,4‐Thiadiazole Derivatives

Some novel [1,2,4]triazolo[3,4‐b][1,3,4]thiadiazole derivatives were synthesized from aryl acetic acids. All the synthesized derivatives were selected for the screening of antibacterial potential against Gram‐positive bacteria [Staphylococcus aureus (MTCC 3160) and Micrococcus luteus (MTCC 1538)] and Gram‐negative bacteria [Escherichia coli (MTCC 1652) and Pseudomonas aeruginosa (MTCC 424)] and antifungal potential against Aspergillus niger (MTCC 8652) and Candida albicans (MTCC 227), and free radical scavenging activity through 2,2‐diphenyl‐2‐picrylhydrazyl hydrate method. The compounds TH‐4 , TH‐13 , and TH‐19 were found to be more potent antimicrobial agents compared to standard drugs. The compounds TH‐3 , TH‐9 , and TH‐18 also showed significant antimicrobial activity. The compound TH‐13 showed antioxidant activity with IC₅₀ value better than the standard compound. The structures of all the synthesized compounds were confirmed by Fourier transform infrared, ¹H‐NMR, liquid chromatography–mass spectrometry, and CHN analyzer.     

Convenient Synthesis and Biological Activity of Mono and Diacyl 2,5‐Dimercapto‐1,3,4‐thiadiazole Derivatives

New derivatives of 2,5‐dimercapto‐1,3,4‐thiadiazole substituted both at one or two exocyclic sulfur atoms with a series of aroyl or ethoxycarbonyl groups were synthesized in reactions of 2,5‐dimercapto‐1,3,4‐thiadiazole salts with appropriate acid chlorides or ethyl chloroformate in mild conditions. The products were characterized by spectroscopy (¹H NMR, ¹³C NMR, IR, and HRMS). Some from the synthesized compounds were screened in vitro and in vivo for antibacterial and antifungal activities against a panel of reference strains of microorganisms. The study revealed that ethyl S‐(5‐mercapto‐1,3,4‐thiadiazol‐2‐yl) carbonothioate seems to be the most active and versatile compound against Gram‐positive bacteria, Gram‐negative bacteria, and plant pathogenic fungi.