Synthesis of novel pyrroles and fused pyrroles as antifungal and antibacterial agents.
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ABSTRACT:
SUBMITTER: Abd El-Hameed RH
PROVIDER: S-EPMC8491725 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThiazolidine-2, 4-diones (TZDs) have become a pharmacologically important class of heterocyclic compounds since their introduction in the form of glitazones into the clinical use for the treatment of type 2 diabetes. TZDs lower the plasma glucose levels by acting as ligands for gamma peroxisome proliferators-activated receptors. In addition, this class of heterocyclic compounds possesses various other biological activities such as antihyperglycemic, antimicrobial, anti-inflammatory, anticonvulsant, insecticidal, etc. TZDs are also known for lowering the blood pressure thereby reducing the chances of heart failure and micro-albuminuria in the patients with type 2 diabetes.ResultsWe have described herein the synthesis of three series of compounds, namely, ethyl 2-((Z)-5-((3-aryl-1-phenyl-1H-pyrazol-4-yl)methylene)-2, 4-dioxothiazolidin-3-yl)acetates (4), methyl 2-((Z)-5-((3-aryl-1-phenyl-1H-pyrazol-4-yl)methylene)-2, 4-dioxothiazolidin-3-yl)acetates (5), and 2-((Z)-5-((3-aryl-1-phenyl-1H-pyrazol-4-yl)methylene)-2, 4-dioxothiazolidin-3-yl)acetic acids (6). The compounds 4 and 5 were synthesized by Knoevenagel condensation between 3-aryl-1-phenyl-1H-pyrazole-4-carbaldehydes (1) and ethyl/methyl 2-(2, 4-dioxothiazolidin-3-yl)acetates (3, 2) in alcohol using piperidine as a catalyst. The resultant compounds 4 and 5 having ester functionality were subjected to acidic hydrolysis to obtain 6. All the new compounds were tested for their in vitro antibacterial and antifungal activity.ConclusionsKnoevenagel condensation approach has offered an easy access to new compounds 4-6. Antimicrobial evaluation of the compounds has shown that some of the compounds are associated with remarkable antifungal activity. In case of antibacterial activity, these were found to be effective against Gram-positive bacteria. However, none of the compounds were found to be effective against Gram-negative bacteria.
| S-EPMC3320062 | biostudies-literature
Project description:In the present work, monoacylglycerol derivatives, i.e., 1-monomyristin, 2-monomyristin, and 2-monopalmitin were successfully prepared from commercially available myristic acid and palmitic acid. The 1-monomyristin compound was prepared through a transesterification reaction between ethyl myristate and 1,2-O-isopropylidene glycerol, which was obtained from the protection of glycerol with acetone, then followed by deprotection using Amberlyst-15. On the other hand, 2-monoacylglycerol derivatives were prepared through enzymatic hydrolysis of triglycerides in the presence of Thermomyces lanuginosa lipase enzymes. The synthesized products were analyzed using fourier transform infrared (FTIR) spectrophotometer, gas or liquid chromatography-mass spectrometer (GC-MS or LC-MS), and proton and carbon nuclear magnetic resonance (¹H- and 13C-NMR) spectrometers. It was found that monomyristin showed high antibacterial and antifungal activities, while 2-monopalmitin did not show any activity at all. The 1-monomyristin compound showed higher antibacterial activity against Staphylococcus aureus and Aggregatibacter actinomycetemcomitans and also higher antifungal activity against Candida albicans compared to the positive control. Meanwhile, 2-monomyristin showed high antibacterial activity against Escherichia coli. The effect of the acyl position and carbon chains towards antibacterial and antifungal activities was discussed.
| S-EPMC6320884 | biostudies-other
Project description:The rise and emergence of resistance to antifungal drugs by diverse pathogenic fungal strains have resulted in an increase in demand for new antifungal agents. Various heterocyclic scaffolds with different mechanisms of action against fungi have been investigated in the past. Herein, we report the synthesis and antifungal activities of 18 alkylated mono-, bis-, and trisbenzimidazole derivatives, their toxicities against mammalian cells, as well as their ability to induce reactive oxygen species (ROS) in yeast cells. Many of our bisbenzimidazole compounds exhibited moderate to excellent antifungal activities against all tested fungal strains, with MIC values ranging from 15.6 to 0.975?g/mL. The fungal activity profiles of our bisbenzimidazoles were found to be dependent on alkyl chain length. Our most potent compounds were found to display equal or superior antifungal activity when compared to the currently used agents amphotericin B, fluconazole, itraconazole, posaconazole, and voriconazole against many of the strains tested.
| S-EPMC4955774 | biostudies-literature
Project description:The rise of antimicrobial-resistant phenotypes and the spread of the global pandemic of COVID-19 are worsening the outcomes of hospitalized patients for invasive fungal infections. Among them, candidiases are seriously worrying, especially since the currently available drug armamentarium is extremely limited. We recently reported a new class of macrocyclic amidinoureas bearing a guanidino tail as promising antifungal agents. Herein, we present the design and synthesis of a focused library of seven derivatives of macrocyclic amidinoureas, bearing a second phenyl ring fused with the core. Biological activity evaluation shows an interesting antifungal profile for some compounds, resulting to be active on a large panel of Candida spp. and C. neoformans. PAMPA experiments for representative compounds of the series revealed a low passive diffusion, suggesting a membrane-based mechanism of action or the involvement of active transport systems. Also, compounds were found not toxic at high concentrations, as assessed through MTT assays.
| S-EPMC8830944 | biostudies-literature
Project description:A series of novel thienopyridines and pyridothienoquinolines (3a,b-14) was synthesized, starting with 2-thioxo-1,2-dihydropyridine-3-carbonitriles 1a and 1b. All compounds were evaluated for their in vitro antimicrobial activity against six bacterial strains. Compounds 3a,b, 4a, 5b, 6a,b, 7a, 9b, 12b, and 14 showed significant growth inhibition activity against both Gram-positive and Gram-negative bacteria compared with the reference drug. The most active compounds (4a, 7a, 9b, and 12b) against Staphylococcus aureus were also tested for their in vitro inhibitory action on methicillin-resistant Staphylococcus aureus (MRSA). The tested compounds showed promising inhibition activity, with the performance of 12b being equal to gentamicin and that of 7a exceeding it. Moreover, the most promising compounds were also screened for their Escherichia coli DNA gyrase inhibitory activity, compared with novobiocin as a reference DNA gyrase inhibitor. The results revealed that compounds (3a, 3b, 4a, 9b, and 12b) had the highest inhibitory capacity, with IC50 values of 2.26-5.87 µM (that of novobiocin is equal to 4.17 µM). Docking studies were performed to identify the mode of binding of the tested compounds to the active site of E. coli DNA gyrase B.
| S-EPMC6832920 | biostudies-literature
Project description:Background and purpose:A group of thiosemicarbazones were prepared and their structures were confirmed by spectroscopic methods such as IR and H-NMR, mass spectrometry and also analytical method like elemental analysis. The synthesized semicarbazones were then assessed for their inhibitory activity against bacterial strains including Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermidis, Bacillus cereus, Salmonella species, Enterobacter faecalis, methicillin-resistant Staphylococcus aureus, and fungi such as Candida albicans and Aspergillus niger. Experimental approach:The schiff bases of isatin (2a-j) were prepared by a condensation reaction between thiosemicarbazide and substituted N-aryl isatins leading to the desired thiosemicarbazones with exquisite purity. Findings / Results:The results disclosed that all compounds have noticeable inhibitory activity. Compounds 2a, 2b, 2c, 2g, and 2h were among the most potent derivatives against Gram negative bacteria and fungi. Besides, the activity of theses compounds were tested against Mycobacterium bovis bacillus Calmette-Guerin (M. bovis BCG). The antimycobacterial activity indicated compounds 2e and 2j are highly active against M. bovis BCG (minimum inhibitory concentration < 3.9 ?g/mL). Among fluorinated structures, compounds 2a and 2j showed the best activities against M. bovis BCG. Conclusion and implications:To sum up, amongst the 10 synthesized compounds, fluorinated derivatives exhibited remarkable activities against both gram negative strains and candida albicans microorganism. Therefore, they should be considered as a clue for further modifications in next investigations. Furthermore, inserting a small/medium size halogen atom with electron-withdrawing and lipophilic properties increases anti- salmonella activity of these compounds and moreover 2-halogenated semithiocarbazones presented promising antimycobacterial activity.
| S-EPMC7540816 | biostudies-literature
Project description:A two-step, one-pot synthesis of fused pyrroles is realized by firstly condensing an N-alkynylhydroxammonium salt with a readily enolizable ketone under mild basic conditions and then subjecting the reaction mixture to a gold catalyst, which triggers a cascade reaction involving a facile initial [3.3]-sigmatropic rearrangement of the gold-catalysis product, that is, an N,O-dialkenylhydroxamine. The reaction provides a facile access to polycyclic pyrroles in moderate to good yields.
| S-EPMC4098939 | biostudies-literature
Project description:The global health concern of antimicrobial resistance has harnessed research interest to find new classes of antibiotics to combat disease-causing pathogens. In our studies, 3-halobenzo[b]thiophene derivatives were synthesized and tested for their antimicrobial activities using the broth microdilution susceptibility method. The 3-halo substituted benzo[b]thiophenes were synthesized starting from 2-alkynyl thioanisoles using a convenient electrophilic cyclization methodology that utilizes sodium halides as the source of electrophilic halogens when reacted along with copper(II) sulfate. This environmentally benign methodology is facile, uses ethanol as the solvent, and results in 3-halo substituted benzo[b]thiophene structures in very high yields. The cyclohexanol-substituted 3-chloro and 3-bromobenzo[b]thiophenes resulted in a low MIC of 16 µg/mL against Gram-positive bacteria and yeast. Additionally, in silico absorption, distribution, metabolism, and excretion (ADME) properties of the compounds were determined. The compounds with the lowest MIC values showed excellent drug-like properties with no violations to Lipinski, Veber, and Muegge filters. The time-kill curve was obtained for cyclohexanol-substituted 3-chlorobenzo[b]thiophenes against Staphylococcus aureus, which showed fast bactericidal activity at MIC.
| S-EPMC8780876 | biostudies-literature
Project description:BackgroundPlant fungi (e.g., Pellicularia sasakii, Gibberella zeae, Fusarium oxysporum, and Cytospora mandshurica and Phytophthora infestans) and bacteria (e.g., Ralstonia solanacearum) are extremely difficult to manage in agricultural production. The high incidence of plant mortality and the lack of effective control methods make P. sasakii and R. solanacearum two of the world's most destructive plant pathogens. Pathogenic fungi and bacteria are responsible for billions of dollars in economic losses worldwide each year. Thus, we designed an active amide structure and synthesized a series of novel amide derivatives containing a triazole moiety to discover new bioactive molecules and pesticides that can act against fungi and bacteria.ResultsA series of amide derivatives containing a triazole moiety were synthesized. All the obtained compounds were characterized through proton and carbon nuclear magnetic resonance spectroscopy, infrared spectroscopy, and elemental analysis. Preliminary antifungal activity test showed that some of the synthesized compounds exhibited moderate antifungal activity against P. sasakii, G. azeae, F. oxysporum, C. mandshurica, and P. infestans at 50 mg/L. Compound 4u displayed more potent antifungal activity against P. sasakii and G. azeae than hymexazol. Preliminary antibacterial activity results showed that some of the synthesized compounds exhibited high anti-bacterial activity against R. solanacearum at 200 mg/L. Compounds 4m and 4q displayed high antibacterial activity against R. solanacearum, with 71% and 65% inhibitory rates, respectively.ConclusionsA series of novel amide derivatives containing 1,2,4-triazole moiety were synthesized through the reaction of intermediate 3 with different acyl chlorides and anhydrous potassium carbonates in anhydrous tetrahydrofuran at 50°C, using 2,4-dichloroacetophenoneas as a starting material. The title compounds exhibited high inhibitory effects against P. sasakii, R. solanacearum, and G. azeae.
| S-EPMC3598687 | biostudies-literature
Project description:A series of new benzofuryl α-azole ketones was synthesized and reduced by asymmetric transfer hydrogenation (ATH). Novel benzofuryl β-amino alcohols bearing an imidazolyl and triazolyl substituents were obtained with excellent enantioselectivity (96-99%). The absolute configuration (R) of the products was confirmed by means of electronic circular dichroism (ECD) spectroscopy supported by theoretical calculations. Selected benzofuryl α-azole ketones were also successfully asymmetrically bioreduced by fungi of Saccharomyces cerevisiae and Aureobasidium pullulans species. Racemic and chiral β-amino alcohols, as well as benzofuryl α-amino and α-bromo ketones were evaluated for their antibacterial and antifungal activities. From among the synthesized β-amino alcohols, the highest antimicrobial activity was found for (R)-1-(3,5-dimethylbenzofuran-2-yl)-2-(1H-imidazol-1-yl)ethan-1-ol against S. aureus ATCC 25923 (MIC = 64, MBC = 96 μg mL-1) and (R)-1-(3,5-dimethylbenzofuran-2-yl)-2-(1H-1,2,4-triazol-1-yl)ethan-1-ol against yeasts of M. furfur DSM 6170 (MIC = MBC = 64 μg mL-1). In turn, from among the tested ketones, 1-(benzofuran-2-yl)-2-bromoethanones (1-4) were found to be the most active against M. furfur DSM 6170 (MIC = MBC = 1.5 μg mL-1) (MIC-minimal inhibitory concentration, MBC-minimal biocidal concentration).
| S-EPMC7560283 | biostudies-literature