Synthesis and Antimicrobial Activities of Novel 2‐[substituted‐1H‐pyrazol‐4‐yl] Benzothiazoles,Benzoxazoles, and Benzimidazoles

In an endeavor to find a new class of antimicrobial agents, a series of novel substituted benzimidazole, benzoxazole, and benzothiazole derivatives 6 containing pyrazole moiety have been synthesized by reaction of 3‐aryl‐4‐formyl pyrazole 4 with substituted phenylenediamine or o‐aminophenol or o‐aminothiophenol 5 . Reaction of phenyl hydrazine or 2‐hydrazinopyridine 1 with substituted acetophenones 2 gave the corresponding hydrazones 3 , which on Vilsmeier–Haack reaction with POCl₃–DMF gave substituted 3‐aryl‐4‐formyl pyrazoles 4 . All final compounds 6a , 6b , 6c , 6d , 6e , 6f , 6g , 6h , 6i , 6j , 6k were evaluated for in vitro antibacterial activities against Escherichia coli and Staphylococcus aureus strains and in vitro antifungal activity against Candida albicans and Aspergillus niger strains by using serial dilution method. The antimicrobial activities were expressed as the minimum inhibitory concentration in µg/mL. The compound containing benzimidazole and benzoxazole moiety gave better antibacterial and antifungal activities than benzothiazole compounds.     

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.     

The chemical constituents from the active fractions of Eleutherine bulbosa with their antimicrobial activity

Abstract

Six compounds including three new polyketide ones named eleubosas A-C (1–3) were isolated from the active frations of Eleutherine bulbosa. Their structures were elucidated by extensive spectroscopic methods, including NMR, MS and IR spectroscopic analyses data. All the isolates were evaluated against three pathogenic bacteria, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, and the results showed that compounds 1 and 2 displayed moderate inhibitory activities against E. coli with MIC values both 12.5?μg/mL, which are consistent with the clinical applications and need further studies.     

Synthesis and antimicrobial activities of 4-aryl-3,4-dihydrocoumarins and 4-arylcoumarins

A new series of 4-aryl-3,4-dihydrocoumarins and 4-arylcoumarins were synthesized by the reaction of substituted cinnamic acids and 3-arylpropiolic acid with the corresponding phenols. These compounds were evaluated for antibacterial activity in vitro. The synthesized compounds displayed different degrees of antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Bacillus dysenteriae, and Candida albicans (a fungus). Compounds with catechol moieties and 7,8-substituted dihydroxyls in the A ring were the most active antimicrobial agents.     

DABCO mediated one pot synthesis of 2-(3-benzyl-2, 6-dioxo-3, 6-dihydropyrimidin-1[2H]-yl)-N-(4-(1, 3-dioxo-1H-benzo [de]isoquinolin-2[3H]-yl) aryl) acetamides as antimicrobial agents

We report herein DABCO mediated one pot synthesis of 2-(3-benzyl-2, 6-dioxo-3,6-dihydropyrimidin-1[2H]-yl)-N-(4-(1,3-dioxo-1H-benzo[de]isoquinolin-2[3H]-yl) aryl) acetamides ( 4a-j ). The silent features of this new one pot synthesis include the shorter reaction time, high yields, simple workup, and simultaneous formation of N-Amide and N-benzyl bonds in the one pot. The newly synthesized compounds ( 4a-j ) were characterized by different spectral techniques such as IR, ¹H-NMR, ¹³C-NMR, HRMS. All the synthesized compounds were evaluated for their anti-bacterial and anti-fungal activities. The anti-bacterial activities results reveal that the compounds 4a , 4g , 4i , and 4j are most active against S. aureus. In the case of B. subtilis the compounds 4a , 4i , and 4j are found to be most active. The compounds 4c , 4e , 4i , and 4j are most active against E. coli. In the case of P. aeruginosa 4a , 4i & 4j are found to be more active. On the other hand, the anti-fungal activity result shows that the compounds 4d , 4f , 4i , and 4j are more active against A. niger. The compounds 4a , 4d , 4i , and 4j are found to be more active against C. albicans.     

Synthesis of Functionalized H‐[1]Benzopyrano[2,3‐b]pyridines by the Friedländer Approach: Antimycobacterial and Antimicrobial Profile

A series of functionalized H‐[1]benzopyrano[2,3‐b]pyridine derivatives were synthesized by the Friedländer reaction of 2‐amino‐4‐oxo‐4H‐chromene‐3‐carbonitriles 1 with malononitrile, ethyl cyanoacetate, or acetophenone (Scheme). The synthesized compounds 2 – 4 were screened for their in vitro activity against antitubercular, antibacterial, and antifungal species (Fig., Table). Among the synthesized compounds, 3c and 4f were the most active with 99% inhibition against Mycobacterium tuberculosis H₃₇Rv, while compounds 2f, 3f , and 4d exhibited 69%, 63%, and 61% inhibition, respectively. The 4‐amino‐7,9‐dibromo‐1,5‐dihydro‐2,5‐dioxo‐2H‐chromeno[2,3‐b]pyridine‐3‐carbonitrile ( 3b ) showed the most potent antibacterial activity against Escherichia coli and Pseudomonas aeruginosa. Several chromeno[2,3‐b]pyridine derivatives showed equal or more potency against Staphylococcus aureus and Candida albicans.     

In vitro antimicrobial activity of extracts and compounds isolated from Cladonia uncialis

Heptane (Hep), diethyl ether (Et₂O), acetone (Me₂CO) and methanolic (MeOH) extracts, as well as ( ? )-usnic acid and squamatic acid, were obtained from thallus of Cladonia uncialis (Cladoniaceae). The antimicrobial activities of these extracts, ( ? )-usnic acid and squamatic acid, were tested against reference strains: Staphylococcus aureus, Escherichia coli and Candida albicans. In addition, Me₂CO extract was analysed against 10 strains of Methicillin-resistant S. aureus (MRSA) isolated from patients. All extracts exerted antibacterial activity against the reference strain S. aureus, comparably to chloramphenicol [minimum inhibitory concentration (MIC) = 5.0 μg/mL]. The Me₂CO extract exhibited the strongest activity against S. aureus (MIC = 0.5 μg/mL), higher than ( ? )-usnic acid, whereas squamatic acid proved inactive. The Me₂CO extract showed potent antimicrobial activity against MRSA (MIC 2.5–7.5 μg/mL). Also no activity of C. uncialis extracts against E. coli and C. albicans was observed.     

Bioactivity and chemical composition of the essential oil from the leaves of Guatteria australis A.St.-Hil

Essential oil from the leaves of Guatteria australis was obtained by hydrodistillation, analyzed by Gas Chromatography coupled to Mass Spectromery (GC–MS) and their antiproliferative, antileishmanial, antibacterial, antifungal and antioxidant activities were also evaluated. Twenty-three compounds were identified among which germacrene B (50.66%), germacrene D (22.22%) and (E)-caryophyllene (8.99%) were the main compounds. The highest antiproliferative activity was observed against NCI-ADR/RES (TGI = 31.08 μg/ml) and HT-29 (TGI = 32.81 μg/ml) cell lines. It also showed good antileishmanial activity against Leishmania infantum (IC₅₀ = 30.71 μg/ml). On the other hand, the oil exhibited a small effect against Staphylococcus aureus ATCC 6538, S. aureus ATCC 14458 and Escherichia coli ATCC 10799 (MIC = 250 μg/ml), as well as small antioxidant activity (457 μmol TE/g) assessed through ORAC_FL assay. These results represent the first report regarding chemical composition and bioactivity of G. australis essential oil.     

Synthesis,Characterization, and Biological Evaluation of Some Tri‐Substituted Imidazole/thiazole Derivatives

A novel compound series of tri‐substituted imidazole/thiazole derivatives ( 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h , 3i ) were prepared by Radziszewski reaction. Benzil ( 1 ), ammonium acetate or ammonium thiocynate, and 1‐phenyl‐3‐(p‐substituted phenyl)‐1H‐pyrazole‐4‐carbaldehyde ( 2a , 2b , 2c , 2d , 2e , 2f , 2g ) were reacted to give the desired product. Synthesized compounds were characterized by elemental analysis (CHNS) and spectral analysis (FTIR, ¹H and ¹³C FT NMR, and LC–MS). All the compounds were screened for their antibacterial, antifungal, and antimycobacterial activities. Antimicrobial activity was evaluated against some bacterial strains such as Escherichia coli (MTCC 443), Pseudomonas aeruginosa (MTCC 1688), Staphylococcus aureus (MTCC 96), Streptococcus pyogenes (MTCC 442), and the H₃₇Rv strain of Mycobacterium tuberculosis, and the fungal activity was observed against strains, for example, Candida albicans (MTCC 227), Aspergillus niger (MTCC 282), and Aspergillus clavatus (MTCC 1323). All the synthesized compounds were found to possess moderate to excellent activity against the above selected strains.     

Chemical composition and antibacterial activity of Tussilago farfara (L.) essential oil from Quebec,Canada

Abstract

The chemical composition of Tussilago farfara L. essential oil from the Saguenay-Lac-St-Jean region of Quebec, Canada was analyzed by gas chromatography–flame ionisation detector (GC-FID) and gas chromatography–mass spectrometry (GC-MS), and the antibacterial activity of the oil was tested against Escherichia coli and Staphylococcus aureus. Forty-five (45) compounds were identified from the GC profile. The main components were 1-nonene (40.1%), α-phellandrene (26.0%) and ρ-cymene (6.6%). The essential oil demonstrated antibacterial activity against E. coli (MIC₅₀ = 468 µg·mL^?1; MIC₉₀ = 6869 µg·mL^?1) and S. aureus (MIC₅₀ = 368 µg·mL^?1; MIC₉₀ = 773 µg·mL^?1). Dodecanoic acid was found to be active against both bacteria having a MIC₅₀ and MIC₉₀ of 16.4 µg·mL^?1 and 95 µg·mL^?1, respectively for E. coli and a MIC₅₀ and MIC₉₀ of 9.8 µg·mL^?1 and 27.3 µg·mL^?1, respectively for S. aureus. In addition, 1-decene and (E)-cyclodecene were also found to be active against E. coli.     

A green synthesis of quinoline-4-carboxylic derivatives using p-toluenesulfonic acid as an efficient organocatalyst under microwave irradiation and their docking,molecular dynamics,ADME-Tox and biological evaluation

P-Toluenesulfonic acid, being an efficient, nonhazardous, and fast accessible organocatalyst, was used for the preparation of quinoline-4-carboxylic acid derivatives via a one-pot three-component reaction of aromatic benzaldehyde, substituted aniline, and pyruvic acid under microwave irradiation. After completion of the reaction, the pure products were isolated by column chromatography. Here, to achieve the desired synthesis, various catalytic and solvent conditions were applied to perform a comparison study. We are using higher yield, simple work-up process, avoiding the use of hazardous organic solvents, short reaction time and higher advantages of the present protocol in the study. Biological activities of synthesized compounds were tested against various antibacterial, antifungal, antimalarial, and antituberculosis strains. Compounds 4a and 4c (MIC 50 μg/mL) and compounds 4d and 4n (MIC 62.5 μg/mL) were found active against the Escherichia coli strain, compounds 4c and 4p (MIC 25 μg/mL) were found active against the Staphylococcus aureus strain, and compounds 4c and 4d were found active against the Plasmodium falciparum strain. Molecular docking revealed that ligands and proteins fitted exactly in the binding pocket and had significant correlation with the biological activity. We have also tested molecular dynamics and ADME-Tox parameters for the synthesized compounds.     

Synthesis and Antimicrobial Evaluation of 1,4-Naphthoquinone Derivatives as Potential Antibacterial Agents

1,4-Naphthoquinones are an important class of compounds present in a number of natural products. In this study, a new series of 1,4-naphthoquinone derivatives were synthesized. All the synthesized compounds were tested for in vitro antimicrobial activity. In this present investigation, two Gram-positive and five Gram-negative bacterial strains and one pathogenic yeast strain were used to determine the antibacterial activity. Naphthoquinones tested for its antibacterial potencies, among seven of them displayed better antimicrobial activity against Staphylococcus aureus (S. aureus; 30–70 μg/mL). Some of the tested compounds showed moderate to low antimicrobial activity against Pseudomonas aeruginosa (P. aeruginosa) and Salmonella bongori (S. bongori; 70–150 μg/mL). In addition, most active compounds against S. aureus were evaluated for toxicity to human blood cells using a hemolysis assay. For better understanding, reactive oxygen species (ROS) generation, time-kill kinetic study, and apoptosis, necrosis responses were investigated for three representative compounds.     

Synthesis and properties of some 2,3‐disubstituted 6‐fluoro‐7‐(4‐methyl‐1‐piperazinyl)quinoxalines

The 2,3‐disubstituted 6‐fluoro‐7‐(4‐methyl‐1‐piperazinyl)‐quinoxalines ( 3–11 ) were synthesized for bioassay via reaction of 1.2‐diamino‐4‐fluoro‐5‐(4‐methyl‐1‐piperazinyl)benzene (2) with the appropriate 1,2‐dicarbonyl compounds. However, none of the tested compounds 3–11 showed significant in vitro activ ity against E. coli ATCC11229, S. aureus ATCC6538 and C.albicans SATCC10231.     

Encapsulation of Pd(II) by N4 and N2O2 macrocyclic ligands: their use in catalysis and biology

New macrocyclic Schiff base Pd(II) compounds were synthesized by treating N₄ and N₂O₂ macrocycles with palladium chloride in a 1 : 1 ratio. The resulting macrocyclic compounds were characterized by elemental, IR, ¹H-NMR, ¹³C-NMR, mass, molar conductance, magnetic susceptibility, electronic spectra, and thermal analysis. These compounds were used as catalysts in the development of an efficient catalytic method for reduction of organic substrates having nitro, olefinic, acetylenic, and aldehyde groups under mild reaction conditions. The biological activities of all the macrocycles and macrocyclic Pd(II) compounds have been tested against gram positive (Bacillus subtilis and Staphylococcus aureus) and gram negative (Escherichia coli and Klebsiella pneumonia) bacteria and found to be more active than commercially available antibacterial drugs like Streptomycin and Ampicillin.     

Synthesis and antimycobacterial screening of new 4-(4-(1-benzyl-1H-1,2,3-triazol-4-yl)-1-phenyl-1H-pyrazol-3-yl)quinoline derivatives

A new series of 4-(4-(1-benzyl-1H-1,2,3-triazol-4-yl)-1-phenyl-1H-pyrazol-3-yl)quinoline ( 6a-t ) have been synthesized by a click reaction of 4-(4-ethynyl-1-phenyl-1H-pyrazol-3-yl)quinoline ( 4a-d ) with a substituted benzyl azide ( 5a-e ). The starting alkyne derivatives 4a-d are obtained from Bestmann-Ohira reaction of 1-phenyl-3-(quinolin-4-yl)-1H-pyrazole-4-carbaldehyde and dimethyl(1-diazo-2-oxopropyl)phosphonate. The newly synthesized compounds are screened against M. tuberculosis H37Ra dormant and active, Escherichia coli, Pseudomonas fluorescence, Staphylococcus aureus and Bacillus subtilis strains at 30 μg/mL concentration. Most of the screened compounds showed good to moderate antibacterial activity against S. aureus, B. subtilis, and Mycobacterium tuberculosis H37Ra strains. The synthesized derivatives of quinolinyl-pyrazole-4-carbaldehyde and quinolinyl-pyrazole-4-ethyne reportd good to moderate activity against both strains of M. tuberculosis H37Ra. Ten derivatives of quinolinyl-pyrazole presented good activity against B. subtilis. These results suggested that further optimization and development of quinolinyl-pyrazolyl-1,2,3-triazole moeity could serve as lead compounds for antimycobacterial activity.     

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.     

In vitro pharmacological screening of three newly synthesised pyrimidine derivatives

The antibacterial and antifungal activities of three new pyrimidine derivatives, namely, 2,6-bis(4,6-dimethylpyrimidin-2-ylthio)benzene-1,4-diol (1),3,5-bis(4,6-dimethylpyrimidin-2-ylthio)-2-methylbenzene-1,4-diol (2) and 3,5-bis(4,6-dimethylpyrimidin-2-ylthio)-2-methoxybenzene-1,4-diol (3), synthesised by electrochemical method are presented here. The compounds were screened for their activities against Gram-positive and Gram-negative bacteria, Bacillus subtilis, Staphylococcusaureus, Escherichia coli and a pathogenic fungus Aspergillus niger. The results show that these compounds have significant activity against these bacteria and fungus. The minimum inhibitory concentration of compound 1 was determined as 62.5 μg/mL against B. subtilis, 125 μg/mL against E. coli and 250 μg/mL against S. aureus establishing its promising activities higher than susceptible ranges.     

Microwave-assisted rapid and efficient synthesis of chromene-fused pyrrole derivatives through multicomponent reaction and evaluation of antibacterial activity with molecular docking investigation

The current study aimed to identify a new strategy of FeCl₃ catalyzed multicomponent synthesis of substituted 2H-chromene–fused pyrrole derivatives. A series of chromene-based pyrrole prepared by employing an array of 3-nitro-2H-chromenes, aniline, and acetylacetone in toluene under microwave irradiation. Using FeCl₃ as a prompt catalyst and microwave irradiation to synthesize 2H-chromene–fused pyrrole motifs significantly reduces the reaction time and facilitates to high yields (83%-95%). Structure of all synthesized compounds analyzed by spectroscopic analysis. One-pot reaction, short reaction period, and simple experimental procedure are the fascinating properties associated with this protocol. The in vitro antibacterial activity of the entire series was assessed against Staphylococcus aureus and Escherichia coli. Out of all the compounds, 15b and 15h revealed most excellent potency against both the bacterial strains relative to the reference gentamicin. Docking study was employed to determine the possible binding orientation of DNA gyrase with the active sites of chromene-fused pyrrole analog. The docking results show that compounds 15b and 15h have higher binding affinity with energy −8.00 and −8.80 kcal/mol. These results illuminate the mode of binding progression and provide an esteemed pathway for the design and the structural modification of chromene-fused pyrroles as a newly advanced class of antibacterial agent.     

Synthesis,molecular docking studies,and absorption,distribution, metabolism,and excretion prediction of novel sulfonamide derivatives as antibacterial agents

A series of novel sulfonamide‐amide derivatives were synthesized from 3‐(2,4 dichlorophenylamino)‐3‐oxopropane‐1‐sulfonylchloride and a variety of amines under solvent‐free conditions at room temperature. 3‐(2,4‐dichlorophenylamino)‐3‐oxopropane‐1 sulfonylchloride was synthesized in four steps starting from 2,4‐dichloroaniline and chloropropanoic acid in good yield and purity. The synthesized compounds were screened for their in vitro antibacterial activity against Escherichia coli (ATCC 25922) and Staphylococcus aureus (ATCC 29213). Molecular docking of sulfonamide derivatives into S. aureus tyrosyl‐tRNA synthetase (TyrRS)‐active site was also performed and among these, 5m and 5g tightly fit the active sites that might be inhibitors of TyrRS for further investigations. Also in the silico metabolism profile, drug‐like properties and absorption, distribution, metabolism, excretion and toxicity (ADMET) of the title compounds were calculated by the preADMET server.     

新型5-(对氯苯基)-3-(邻，对-二氯苯基)-4，5-二氢吡唑肟酯衍生物的合成，结构表征及抗菌活性

合成了10个未见文献报道的1-(5-(2-氯苯基)-3-(2,4-二氯苯基)-4,5-二氢-N-吡唑肟酯类衍生物,并经过元素分析、HRMS、核磁共振氢谱对其结构进行了表征。对新合成的化合物进行了初步抗Bacillus subtilis, Staphylococcus aureus, Escherichia coli 和 Pseudomonas aeruginosa生物活性测试,结果表明:化合物7c 和7f对供试病菌具有较好的体外杀灭活性,其MIC值达到1.562 μg/mL;化合物7c ,7d和7f 具有中等的抑制DNA回旋酶活性(IC₅₀ = 1.6~2.5 µg/mL)。在生物活性结果的基础上对系列化合物的构效关系进行了初步的探讨。