Synthesis and antibacterial activity of novel [1,2,4]triazolo [3,4-h][1,8]naphthyridine-7-carboxylic acid derivatives

Novel tricyclic fluoroquinolones,[1,2,4]triazolo[3,4-h][1,8]naphthyridine-8-one-7-carboxylic acid derivatives 4a-4h bearing carrying a functional Mannich-base moiety at the C-8 position,were synthesized and evaluated for their antimicrobial activity.The results showed that some compounds with a piperazine side chain exhibited comparable or better antibacterial activity than comparator cirprofloxacin.Furthermore,the targeted compounds also displayed a broad spectrum of activity against resistant strains including both Gram-negative and Gram-positive bacteria.In particular,compound 4h showed an MIC of 0.25 μg/mL in antibacterial assay against multiple drug-resistant Escherichia coli,which represents an about 30-fold increase of potency compared to ciprofloxacin.Thus,their excellent antibacterial activity against resistant strains suggests that triazole-fused fluoroquinolones warrant further optimization as novel anti-infective chemotherapies.     

CAN catalyzed one-pot synthesis and docking study of some novel substituted imidazole coupled 1,2,4-triazole-5-carboxylic acids as antifungal agents

The present work describes a facile,one-pot three component synthesis of a series of 3-[(4,5-diphenyl-2-substituted aryl/heteryl)-1H-imidazol-1-yl]-1H-1,2,4-triazole-5-carboxylic acid derivatives M(1-15).Benzil,aromatic aldehydes and 3-amino-l,2,4-triazole-5-carboxylic acid was refluxed in ethanol using cerric ammonium nitrate(CAN) as a catalyst to give the title compounds in good yields.The compounds were evaluated for their in vitro antifungal and antibacterial activity.Compounds M1,M9,and M15 were found to be equipotent against Candida albicans when compared with fluconazole.Compounds M2.M5,and M14 showed higher activity against Streptococcus pneumoniae.Escherichia coli and Streptococcus pyogenes,respectively,compared with ampicillin.Docking study of the newly synthesized compounds was performed,and the results showed good binding mode in the active sites of C albicans enzyme cytochrome P450 lanosterol 14α-demethylase.The results of in vitro antifungal activity and docking study showed that synthesized compounds had potential antifungal activity and can be further optimized and developed as a lead compound.     

Novel dihydropyrazole derivatives linked with multi（hetero）aromatic ring： Synthesis and antibacterial activity

Eight novel heterocycle-substituted dihydropyrazole derivatives were synthesized and characterized by ESI-MS,~1H NMR and ~(13)C NMR.All of the compounds have been screened for their antibacterial potential in vitro against Bacillus subtilis, Staphylococcus aureus,Escherichia coli and Pseudomonas aeruginosa.The results show that compounds 9b,9g and 9h displayed significant activity with MIC values in the range of 0.39-1.562μg/mL against B.subtilis.     

Study on the synthesis and antimicrobial activity of novel cationic porphyrins

A novel series of quaternary ammonium cationic derivatives based on tetrapyridyl-porphyrin was synthesized.All the compounds were evaluated for their in vitro antibacterial activities against S.aureus,E.coli and P.aeruginosa,and antifungal activities against C.albicans,where microorganisms were exposed and unexposed to the irradiation.The results revealed that some of these compounds,especially,3a and 4a displayed satisfactory antibacterial activity against Gram-positive bacteria S.aureus and moderate an...     

Synthesis,antimicrobial, antiquorum-sensing and cytotoxic activities of new series of benzothiazole derivatives

New series of benzothiazole derivatives were designed and synthesized. The newly synthesized compounds were screened for their antibacterial activity against Escherichia coli, Staphylococcus aureus and Bacillus cereus. Compounds 6j and 6o showed the highest activity against E. coli and S. aureus. The antifungal activity of these compounds was also tested against Candida albicans and Aspergillus fumigatus293. Compounds 4c, 4g and 6j exhibited the highest activity against C. albicans. In addition, compounds4 a and 6j displayed promising activity against A. fumigatus 293. The same compounds were examined for their antiquorum-sensing activity against Chromobacterium violaceum ATCC 12472, whereas compounds4 a, 6j and 6p showed moderate activity. The in vitro cytotoxicity testing of the synthesized compounds was performed against cervical cancer(Hela) and kidney fibroblast cancer(COS-7) cell lines. Results indicated that all tested compounds have IC50 values 50 mmol/L against both cell lines. Molecular properties, toxicities, drug-likeness, and drug score profiles of compounds 4a–c, 5a, 6g,h, 6j, 6l, 6o and7 c,d were also assessed.     

Action of the Selenomorpholine Compounds on the Bacterium Growth by Microcalorimetry

The action of β-(N-selenomorpholine) ethyl phenyl ketone hydrochloride and 4-(N-selenomorpholine)-2-butanone hydro-chloride on Escherichia coli and Staphylococcus aureus was studied by microcalorimetry,Differences in their capacities to affect the metabolism of this bacterium were observed.The kinetics shows that the selenomorpholine compounds had action on the metabolism process of Escherichia coli and Staphylococcus aureus.The rate constant (k) of the studied bacterium in the presence of the drugs are concentration-dependant.The growth rate constants decrease with an increase in the mass of the selenomorpholine compounds ,but their relationship is different.As deduced from the rate constant(k) of the studied bacterium(in log phase )and the half inhibitory concentration (IC50),the experimental results reveal that the studied selenomorpholine compounds all have good antibiotic activity and better antibacterial activity on Staphylcoccus aureus than on Escherichia coli.     

两种希夫碱对大肠杆菌抗菌活性的微量热法研究

The microcalorimetric method was used to study the antibacterial activity of two newly synthesized Schiff base compounds （H2L3＇ and H2L3） on Escherichia coli, trying to obtain the action on both of multiplying bacteria and non-multiplying bacteria at one experiment. The metabolic power-time curves of the bacteria treated with the compounds were obtained, and the thermokinetic parameters were analyzed, from which the antibacterial activities of these compounds were evaluated. The results showed that both of the two compounds have good activity on aerobic multiplying metabolism of E. coli, with the value of ICso 75.8 and 168.8 mg/L respectively, but have not effective action on fermentation metabolism of E. coli. The action of the compounds on the non-multiplying metabolism was investigated by taking the heat output of E. coli in the stationary phase as the guideline of the activity. The value of MSCso （minimum stationary-cidal concentration 50） of them is 118 and 187.5 mg/L, respectively. So, H2L^3 has stronger antibacterial action on E. coli than H2L^3 either for multiplying bacteria or non-multiplying bacteria, and their activity on the aerobic multiplying bacteria of E. coil is mainly shown. It does strongly suggest that the calorimetric method should play an important role in the fight against the drug-resistant bacteria.     

Synthesis and antitumor activity of heterocyclic acid ester derivatives of 20S-camptothecins

A series of heterocyclic acid esters of camptothecins as new compounds had been synthesized by acylation method,their in vitro and in vivo antitumor activities were evaluated.The cytotoxic results showed that 6 possessed the best efficacy on six human cancer cell lines in the six classes of CPTs' derivatives.In vivo testing results indicated that 9 had better antitumor activity against mouse liver carcinoma H_(22) than topotecan.     

Environmentally Benign Synthesis of 2-Pyrazolines and Cyclohexenones Incorporating Naphthalene Moiety and Their Antimicrobial Evaluation

We reported the environmental benign synthesis of chalcones,2-pyrazolines and cyclohexanones under microwave irradiation.Chalcones were obtained by the condensation of each of 2-hydroxyacetophenone derivatives with a-naphthaldehyde under microwave irradiation.The condensation reactions of each of synthesized chalcones with phenyl hydrazine under microwave irradiation in the presence of dry acetic acid as a cyclizing agent gave 2-pyrazolines.Also,the new cyclohexenone derivatives,valuable intermediates to synthesize fused heterocycles,have been prepared by the cyclocondensation of each of hydroxychalcones with ethyl acetoacetate.The structures of the synthesized compounds were elucidated by infrared（IR） spectrometry,nuclear magnetic resonance（NMR）,mass spectrometry（MS） and elmental analysis.The results indicate that unlike classical heating,microwave irradiation results in higher yields with shorter and cleaner reactions.The synthesized compounds were screened for antimicrobial activity against Staphylococcus aureus,Escherichia coli,Candida Albicans and Aspergillus niger.We clarified the effects of different substituents in the tested compounds on the obtaind antibacterial activities and antifungal activities.     

Ternary Solid Nano Organic/Inorganic Composite of Lanthanum with Acetic Acid and Curcumin/ Hydroxyapatite and Its Antibacterial Activity

Ternary solid complex was synthesized via hybridization of curcumin（Cur）, hydroxyapatite（HAP）, lanthanum（La） and acetic acid（HAc）. The nano-scale hybrid composite of La-Cur/HAP was directly prepared by the wet method. The morphologies and structures of the composite were characterized by scanning electron microscopy （SEM）, infrared（IR） spectroscopy, X-ray diffraction（XRD）, transmission electron microscopy（TEM） and energy dispersive X-ray spectroscopy. The antibacterial activities were tested by methods of minimum inhibitory concentration （MIC） and minimum bactericidal concentration（MBC）. The results show that the size of the La-Cur/HAP composite is less than 100 nm, and the composite exhibits strong bacteriostatic activity against Escherichia coli（E, colt） and Staphylococcus aureus（S, aureus） at low concentrations（in the range of 26-92μg/mL）. The composite can exhibit both of the bacteria and shows higher antibacterial activity against S. aureus than against E. colt. At the same time, La-Cur/HAP shows stronger antibacterial efficiency than ampicillin/HAP.     

Synthesis and Evaluation of Antimicrobial Activity of Some New Hetaryl‐Azoles Derivatives Obtained from 2‐Aryl‐4‐methylthiazol‐5‐carbohydrazides and Isonicotinic Acid Hydrazide

A series of new 1,3,4‐oxadiazole/thiadiazole and 1,2,4‐triazole derivatives have been synthesized starting from 2‐aryl‐4‐methylthiazol‐5‐carbohydrazides and isonicotinic acid hydrazide. All the newly synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, and mass spectrometry. The synthesized compounds were screened for their antibacterial and antifungal activity, assessed as growth inhibition diameter. Some of them showed good antibacterial activity against gram positive Staphylococcus aureus, while the antibacterial activity against Listeria monocytogenes, Escherichia coli, and Salmonella typhymurium and antifungal activity against Candida albicans was modest. None of the tested compounds showed inhibitory activity against gram positive bacteria Enterococcus faecalis and Bacillus cereus and against gram negative bacteria Pseudomonas aeruginosa.     

An Efficient Synthesis and Antibacterial Activity of Pyrido[2,3‐d]Pyrimidine,Chromeno[3,4‐c]Pyridine,Pyridine, Pyrimido[2,3‐c]Pyridazine,Enediamines, and Pyridazine Derivatives

A series of Pyrido[2,3‐d]pyrimidine have been synthesized through a reaction of cyanoacetylurea derivatives with aromatic aldehydes or Arylidines. Reaction of compound 1 with aromatic arylidine derivatives or arylhydrazones gave Chromeno[3,4‐c]pyridine, Pyridine, Pyrimido[2,3‐c]pyridazine, Enediamines, and Pyridazine derivatives. All the synthesized compounds were confirmed by spectral studies and screened for their in antibacterial activity against Staphylococcus aureus (Gram positive) and Escherichia coli (Gram negative) bacterial strains. All the compounds were weak to good active against the tested bacterial strains on comparing with the standard drug gentamicin.     

Synthesis and Antibacterial Activity of 3‐(Substituted arylmethyl)‐4‐acylaminomethyloxazolidin‐2‐ones and Derivatization to Symmetrical Twin‐Drug Type Molecules

In connection with our studies on antibacterial active compounds in the class of new oxazolidinones against Gram‐positive (Staphylococcus aureus) and Gram‐negative (Escherichia coli) strains, some molecular modifications were attempted. In this study, molecular modifications of 4‐aminomethyloxazolidin‐2‐ones ( 3a ) to the corresponding 4‐acylaminomethyloxazolidin‐2‐one derivatives ( 3c–d ) and preparations of the represented twin‐drug type molecules ( 10–14 ) were investigated. Some additional 4‐dialkylaminomethyloxazolidin‐2‐ones ( 2 ) were also synthesized. The synthesized compounds were evaluated for antibacterial activity with Gram‐positive (S. aureus) and Gram‐negative (E. coli) strains.     

Synthesis and in vitro Antibacterial Activities of 5‐(2,3,4,5‐Tetrahydro‐1H‐chromeno[2,3‐d]pyrimidin‐5‐yl)pyrimidione Derivatives

A series of novel 5‐(2,3,4,5‐tetrahydro‐1H‐chromeno[2,3‐d]pyrimidin‐5‐yl)pyrimidione derivatives have been synthesized from substituted salicylaldehydes and barbituric acid or 2‐thiobarbituric acid in water catalyzed by phase transfer catalysis of triethylbenzyl ammonium chloride (TEBA). Elemental analysis, IR, ¹H NMR, and ¹³C NMR elucidated the structures of all the newly synthesized compounds. In vitro antimicrobial activities of synthesized compounds have been investigated against Escherichia coli, Bacillus subtilis, Staphylococcus aureus, and Pseudomonas aeruginosa. These newly synthesized derivatives exhibited significant in vitro antibacterial activity.     

Synthesis,Characterization, and Antimicrobial Screening of 4″‐methyl‐2,2″‐diaryl‐4,2′:4′,5″‐terthiazole Derivatives

A series of novel 4″‐methyl‐2,2″‐diaryl‐4,2′:4′,5″‐terthiazole ( 8a‐p ) derivatives has been synthesized and screened for antibacterial activity against four pathogenic bacteria, Escherichia coli, Pseudomonas flurescence, Staphylococcus aureus, and Bacillus subtilis. Among them, compounds 8a and 8j exhibited excellent antibacterial activity with minimum inhibitory concentration range of 1.0 to 5.3 μg/mL and compounds 8m and 8p exhibited moderate to good antibacterial activity with minimum inhibitory concentration range of 16.9 to 29.7 μg/mL against all tested strains. All the synthesized compounds were screened for their in vitro antifungal activity against Cocinida candida. Most of the compounds reported moderate antifungal activity. This study provides valuable directions to our ongoing endeavor of rationally designing more potent antimicrobial agent.     

Synthesis of Novel Fused Thiazolo[3,2‐a]pyrimidin‐3‐ols and Evaluation for their Antibacterial Activity

A series of novel fused thiazolo[3,2‐a]pyrimidin‐3‐ol derivatives have been synthesized by reaction of fused pyrimidine‐thiones with 4‐substituted phenacyl bromide/3(2‐bromoacetyl)coumarin in refluxing acetic acid with good yields. All the synthesized compounds were confirmed by spectral studies and screened for their in vitro antibacterial activity against Staphylococcus aureus, Bacillus thuringiensis (Gram positive), Escherichia coli, and Klebsiella pneumoniae (Gram negative) bacterial strains. Activity results revealed that all the compounds were weak to good active against the tested bacterial strains on comparing with the standard drug gentamicin.     

Synthesis of New Triazole and Oxadiazole Derivatives of Quinazolin‐4(3H)‐one and Their Antimicrobial Activity

A series of new triazole derivatives of quinazolin‐4(3H)‐one and new oxadiazole derivatives of quinazolin‐4(3H)‐one were synthesized. The newly synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR and mass spectral data. All the newly synthesized compounds were screened for antibacterial activity against Staphylococcus aureus, Bacillus subtilis (gram‐positive bacteria), Escherichia coli, Pseudomonas aeruginosa (gram‐negative bacteria), and antifungal activity was carried out against Candida albicans and Aspergillus niger.     

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.     

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.     

Design,Synthesis and Molecular Modeling of Nonsteroidal Anti‐inflammatory Drugs Tagged Substituted 1,2,3‐Triazole Derivatives and Evaluation of Their Biological Activities

A novel series of 1,4‐disubstituted‐1,2,3‐triazole derivatives 3a – l and 5a – i were one‐pot synthesized via CuAAC‐alkyne click chemistry and evaluated for their antibacterial activity against four organisms and screened for their anticancer activity against human colon cancer cell line HT‐29 and human lung cancer cell line HTB‐29. These hybrid molecules structure elucidation has been performed by IR, ¹H‐NMR, ¹³C‐NMR, and mass spectral analysis. Synthesized nonsteroidal anti‐inflammatory drugs‐triazoles evaluated for their antibacterial activities against bacterial microorganisms Pseudomonas aeruginosa, Escherichia coli, Staphylococcus aureus, and Klebsiella pneumonia. Final compounds 3i , 3c , and 5b showed magnificent broad spectrum activity against P. aeruginosa, K. pneumonia, E. coli, and S. aureus with zone of inhibition values of 20, 15, 17, and 16 mm, respectively. Among the series of compound, 3j showed the best antibacterial activity against all the strains. Further, the compounds 3i and 5a were more cytotoxic than cisplatin against all tested two human cancer cell lines, with 50.8%, and 52.3% and 73.4% and 75.3% of growth, respectively. The synthesized compounds were tested for kinase inhibitory activity against glycogen synthase kinase‐3 protein kinases, in addition, for cytotoxic activity against two different human cancer cell lines.