Synthesis and evaluation of a class of new coumarin triazole derivatives as potential antimicrobial agents

A series of new coumarin-based 1,2,4-triazole derivatives were designed, synthesized and evaluated for their antimicrobial activities in vitro against four Gram-positive bacteria (Staphylococcus aureus, MRSA, Bacillus subtilis and Micrococcus luteus), four Gram-negative bacteria (Escherichia coli, Proteus vulgaris, Salmonella typhi and Shigella dysenteriae) as well as three fungi (Candida albicans, Saccharomyces cerevisiae and Aspergillus fumigatus) by two-fold serial dilution technique. The bioactive assay showed that some synthesized coumarin triazoles displayed comparable or even better antibacterial and antifungal efficacy in comparison with reference drugs Enoxacin, Chloromycin and Fluconazole. Coumarin bis-triazole compounds exhibited stronger antibacterial and antifungal efficiency than their corresponding mono-triazole derivatives.     

Synthesis and activities of naphthalimide azoles as a new type of antibacterial and antifungal agents

Naphthalimide-derived azoles as a new type of antimicrobial agents were synthesized and evaluated for their efficiency in vitro against eight bacteria and two fungi by two fold serial dilution technique. Most title compounds exhibited good antimicrobial potency with low MIC values ranging from 1 to 16 μg/mL. Notably, some synthesized compounds displayed comparable or even better antibacterial and antifungal activities against some tested strains than the reference drugs Orbifloxacin, Chloromycin and Fluconazole, respectively.     

Synthesis,antimicrobial and antifungal activity of a new class of spiro pyrrolidines

A new class of spiro pyrrolidines, dispiro[oxindole-cyclohexanone]pyrrolidines, dispiro[oxindole-tetrahydronaphthalen-1-one]pyrrolidines, dispiro[oxindole-arylidene-cyclohexanone]pyrrolidines, dispiro[oxindole-hexahydro-indazole]pyrrolidines, and spiro[butenolide]pyrrolidines, have been screened for their antibacterial and antifungal activity against ten human pathogenic bacteria and four dermatophytic fungi. They were found to have antimicrobial and antifungal activity compounds against various pathogens except Bacillus subtilis. The spiro pyrrolidinines were synthesized by the regioselective 1,3-dipolar cycloaddition reaction of azomethine ylides generated either from isatin and sarcosine or from aziridine. The azomethine ylide so generated reacted with various dipolarophiles such as 2-arylidene-cyclohexanones, 2-arylidene-tetrahydronapthalen-1-ones, 2,6-bis(arylmethylidene)cyclohexanones and 3-arylidene-5-phenyl- butenolides.     

Design and synthesis of spiro[indole-thiazolidine]spiro[indole-pyrans] as antimicrobial agents

A series of novel spiro[indole-thiazolidine]spiro[indole-pyran] derivatives were synthesized from N-(bromoalkyl)indol-2,3-diones via monospiro-bisindole intermediates; the two indole nuclei being connected via N-(CH(2))(n)-N linker. Synthesized compounds were evaluated for their antimicrobial activities in vitro against three Gram-positive bacteria (Staphylococcus aureus, Bacillus subtilis, and Staphylococcus epidermis), four Gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi, and Klebsiella pneumonia) as well as four fungi (Aspergillus niger, Aspergillus fumigatus, Aspergillus flavus, and Candida albicans) using Cup plate method. Bis spiro-indoles exhibited stronger antibacterial and antifungal efficiency than their corresponding mono spiro-indoles. Compound 10e, the most active derivative was shown to inhibit the growth of all bacterial strains and two fungal strains (A. niger and C. albicans).     

New Benzopyrrole Derivatives: Synthesis and Appraisal of Their Potential as Antimicrobial Agents

A series of twenty compounds ( 23 – 42 ) were synthesized and characterized by spectral studies in order to explore newer antimicrobial compounds. The majority of the synthesized compounds reported significant antimicrobial properties against various pathogenic bacterial and fungal strains with the help of tube dilution method. Significant activities (MIC ranging from 3.9 to 15.62 μg/ml) have been shown against Gram-negative and Gram-positive bacteria with. In contrast, moderate to outstanding antibacterial activity was reported versus Gram-negative bacteria such as E. coli and P. aeruginosa along with Gram-positive bacteria such as S. aureus and B. subtilis. While antifungal activity was moderate to excellent against two fungus strains (Candida tropicalis, Candida glabrata). Compounds 25 and 34 had the utmost activity versus Gram-positive and Gram-negative bacteria too. The antifungal activity of compound 35 was comparable to that of standard. In-silico Molecular docking evaluations were performed for antibacterial and antifungal activities against the target DNA gyrase A (PDB: 1AB4) and 14 alpha-sterol demethylase enzyme (PDB: 1EA1), respectively. The dock score for typicals compounds for antibacterial and antifungal activity were −4.733 and −9.4, respectively. The three-dimensional QSAR examination was carried out by multiple linear regression (SA-MLR) with good predictive power (r2=0.9105, q2=0.8011). Establishment of several interactions between the ligand 25 and 34 and the active site of residue of both receptors, enable the ligand 25 and 34 to be fit well in the pocket of the active site, as seen in Molecular dynamics simulations analysis. Thus, data suggest that these ligands could be further explored as potential precursors to develop antimicrobial drugs.     

Novel berberine triazoles: Synthesis,antimicrobial evaluation and competitive interactions with metal ions to Human Serum Albumin

A series of novel berberine triazoles were synthesized and characterized by IR, NMR, MS and HRMS spectra. All target compounds and their precursors were screened for antimicrobial activities in vitro against four Gram-positive bacteria, four Gram-negative bacteria and two fungal strains. Bioactive assay indicated that most of the prepared compounds exhibited good antibacterial and antifungal activities with low MIC values ranging from 2 to 64 μg/mL, which were comparable to or even better than the reference drugs Berberine, Chloromycin, Norfloxacin and Fluconazole. The competitive interactions between compound 5a and metal ions to Human Serum Albumin (HSA) revealed that the participation of Mg²⁺ and Fe³⁺ ions in compound 5a–HSA association could result in the concentration increase of free compound 5a, shorten the storage time and half-life of compound 5a in the blood, thus improving its antimicrobial efficacy.     

Studies on synthetic and structural characterization of new fluorine substituted phthalides of pharmaceutical interest

An efficient and economical synthesis of some new fluorine substituted phthalides was accomplished from two γ-keto acids, 2-(4-fluorobenzoyl)benzoic acid and 2-(3,5-dinitro-4-flurobenzoyl)benzoic acid. Each acid was reacted with various phenolic compounds in presence of catalytic quantity of concentrated sulphuric acid to get the phthalides. The structures of the synthesized compounds were established on the basis of their elemental analysis, spectral data and chemical reactions. Some of the synthesized phthalides exhibited antibacterial and antifungal activity on antimicrobial screening against human pathogenic bacteria and fungi.     

Synthesis and biological evaluation of a class of quinolone triazoles as potential antimicrobial agents and their interactions with calf thymus DNA

A novel series of quinolone triazoles were synthesized and characterized by IR, NMR, MS and HRMS spectra. All the newly prepared compounds were screened for their antimicrobial activities against seven bacteria and four fungi. Bioactive assay manifested that most of new compounds exhibited good or even stronger antibacterial and antifungal activities against the tested strains including multi-drug resistant MRSA in comparison with reference drugs Norfloxacin, Chloromycin and Fluconazole. The preliminary interactive investigations of compound 6b with calf thymus DNA by fluorescence and UV–vis spectroscopic methods revealed that compound 6b could effectively intercalate DNA to form compound 6b–DNA complex which might block DNA replication and thus exert its antimicrobial activities.     

Studies on synthetic and structural characterization of new fluorine substituted phthalides of pharmaceutical interest

An efficient and economical synthesis of some new fluorine substituted phthalides was accomplished from two γ-keto acids, 2-(4-fluorobenzoyl)benzoic acid and 2-(3,5-dinitro-4-flurobenzoyl)benzoic acid. Each acid was reacted with various phenolic compounds in presence of catalytic quantity of concentrated sulphuric acid to get the phthalides. The structures of the synthesized compounds were established on the basis of their elemental analysis, spectral data and chemical reactions. Some of the synthesized phthalides exhibited antibacterial and antifungal activity on antimicrobial screening against human pathogenic bacteria and fungi.     

Synthesis, characterization and antimicrobial activity of new aliphatic sulfonamide

A series of novel aliphatic sulfonamide derivatives (1-7) were synthesized and characterized by elemental analyses, FT-IR, (1)H NMR, (13)C NMR and LC-MS techniques. All the synthesized compounds were evaluated in vitro as antimicrobial agents against representative strains of Gram-positive (Staphylococcus aureus ATCC 25953, Bacillus cereus ATCC 6633 and Listeria monocytogenes ATCC Li6 (isolate), Gram-negative bacteria (Escherichia coli ATCC 11230) and antifungal agent against Candida albicans (clinical isolate) by both disc diffusion and minimal inhibition concentration (MIC) methods. All these bacteria and fungus studied were screened against some antibiotics to compare with our chemicals' zone diameters. Our aliphatic sulfonamides have highest powerful antibacterial activity for Gram-negative bacteria than Gram-positive bacteria and antibacterial activity decreases as the length of the carbon chain increases.     

Hydrazones of 2-aryl-quinoline-4-carboxylic acid hydrazides: synthesis and preliminary evaluation as antimicrobial agents

A new series of 2-arylquinoline-4-carboxylic acid hydrazide–hydrazones was synthesized using an appropriate synthetic route. All the target compounds were evaluated for their in vitro antimicrobial activity against Staphylococcus aureus as an example for Gram-positive bacteria, Escherichia coli as an example for Gram-negative bacteria, and Candida albicans as a representative of fungi. The minimum inhibitory concentration (MIC) was determined for test compounds as well as for reference standards. Among the compounds tested, compounds having nitro substituents at the arylidene moiety showed the most potent antifungal as well as antibacterial activities against E. coli. Compound 23 displayed an antifungal activity comparable to that of nystatin. However, none of the compounds demonstrated any antibacterial activity against S. aureus. Hydrophobicity of the target compounds correlated weakly with their antibacterial and antifungal activities. The most potent compounds namely, 7, 18, 19, 22, and 23 were assessed for hemolytic toxicity and found to be non-hemolytic up to a concentration of 100 μg/mL. In addition, the most potent compound (23) was evaluated for in vitro cytotoxic activity against various cancer cell lines. This compound was found to display no cytotoxic activity but rather it induces the proliferation rate of Hep-G2 cells.     

Screening of antimicrobial activities in red, green and brown macroalgae from Gran Canaria (Canary Islands, Spain)

Extracts from 44 species of seaweed from Gran Canaria (Canary Islands, Spain) were screened for the production of antibacterial and antifungal compounds against a panel of gram-negative and gram-positive bacteria, mycobacteria, yeasts and fungi. A total of 28 species displayed antibacterial activity, of which six also showed antifungal activity. Asparagopsis taxiformis and Cymopolia barbata were the species with the strongest activities against the broadest spectrum of target microorganisms. All the species with antibacterial activity were active against gram-positive bacteria, whereas only two species, A. taxiformis and Osmundea hybrida, were active against mycobacteria. The production of secondary metabolites with antimicrobial activities by the macroalgae was also studied under different conditions, although no common trend for bioactivity was observed.     

Synthesis and antimicrobial properties of imidazolium and pyrrolidinonium salts

For the purpose of developing new disinfectants and antiseptics, we searched for compounds having high bactericidal activity against gram-positive bacteria, gram-negative bacteria, and fungi. Three different series of quaternary imidazolium and pyrrolidinonium salts were synthesized: series A (1-alkyl-3-methylimidazolium chlorides and bromides); series B (1-alkyl-2-methyl-3-hydroxyethylimidazolium chlorides); and series C (N-alkyl-N-hydroxyethylpyrrolidinonium). Series B and C were newly designed. These three series were tested to evaluate their antibacterial and antifungal properties for the first time. Seven microbial strains were used in the study: Escherichia coli KCTC1924, Salmonella typhimurium KCTC1926, Staphylococcus aureus 209 KCTC1916, Staphylococcus aureus R209 KCTC1928, Bacillus subtilis KCTC1914, Candida albicans KCTC1940, and Chlorella regularis. The antimicrobial efficiency was measured by bacterial and fungal growth inhibition expressed as minimal inhibitory concentration (MIC) values. Series A and B imidazolium salts had very good antimicrobial activity against the examined Gram-negative bacteria, Gram-positive bacteria, and fungi. Also the pyrrolidinonium salt was found to have low MIC for some of tested microorganisms. The antibacterial and antifungal active properties of the salts depend upon the structure of functional groups and the alkyl chain length in the imidazolium and pyrrolidinonium ring. Among the synthesized quaternary imidazolium and pyrrolidinonium salts, the imidazolium salts containing a long alkyl chain and the introduction of a hydroxyethyl chain and methyl group into the imidazolium ring structure leads to broad spectrum active antimicrobial agents which not only have bacteriostatic properties but could be powerful bactericides.     

Synthesis and biological evaluation of novel N-acyl substituted quinolin-2(1H)-one derivatives as potential antimicrobial agents

A series of novel N-acyl substituted quinolin-2(1H)-one derivatives were synthesized and screened in vitro for their antibacterial and antifungal activities by disc diffusion method. All the compounds exhibited moderate to good antimicrobial activities, some of these compounds displayed comparable or better antibacterial or antifungal activities against some tested strains compared to the reference drugs Streptomycin and Fluconazole.     

A new structural alternative in benzo[b]furans for antimicrobial activity

Two series of 2-substituted and three new diacetyl benzofurans were synthesized through palladium-catalyzed reactions and their in vitro antimicrobial spectra were assessed. The compounds demonstrated mild to significant growth inhibition against antibiotic-susceptible standard and clinically isolated strains of Gram-positive and Gram-negative bacteria as well as human fungal pathogens. Ampicillin and kanamycin were used as references for antibacterial screening; nystatin and amphotericin B were used for antifungal screening. Varying substitution at the benzofuran moiety and subsequent antimicrobial screening identified the C-3-acetyl functionality as a new structural alternative for optimal antimicrobial property in the benzofuran class of compounds.     

Bis(N-amidinohydrazones) and N-(amidino)-N′-aryl-bishydrazones: New classes of antibacterial/antifungal agents

The emergence of multidrug-resistant bacterial and fungal strains poses a threat to human health that requires the design and synthesis of new classes of antimicrobial agents. We evaluated bis(N-amidinohydrazones) and N-(amidino)-N′-aryl-bishydrazones for their antibacterial and antifungal activities against panels of Gram-positive/Gram-negative bacteria as well as fungi. We investigated their potential to develop resistance against both bacteria and fungi by a multi-step resistance-selection method, explored their potential to induce the production of reactive oxygen species, and assessed their toxicity. In summary, we found that these compounds exhibited broad-spectrum antibacterial and antifungal activities against most of the tested strains with minimum inhibitory concentration (MIC) values ranging from <0.5 to >500 μM against bacteria and 1.0 to >31.3 μg/mL against fungi; and in most cases, they exhibited either superior or similar antimicrobial activity compared to those of the standard drugs used in the clinic. We also observed minimal emergence of drug resistance to these newly synthesized compounds by bacteria and fungi even after 15 passages, and we found weak to moderate inhibition of the human Ether-à-go-go-related gene (hERG) channel with acceptable IC₅₀ values ranging from 1.12 to 3.29 μM. Overall, these studies show that bis(N-amidinohydrazones) and N-(amidino)-N′-aryl-bishydrazones are potentially promising scaffolds for the discovery of novel antibacterial and antifungal agents.     

Insect immunity. Isolation from the lepidopteran Heliothis virescens of a novel insect defensin with potent antifungal activity

Lepidoptera have been reported to produce several antibacterial peptides in response to septic injury. However, in marked contrast to other insect groups, no inducible antifungal molecules had been described so far in this insect order. Surprisingly, also cysteine-rich antimicrobial peptides, which predominate in the antimicrobial defense of other insects, had not been discovered in Lepidoptera. Here we report the isolation from the hemolymph of immune induced larvae of the lepidopteran Heliothis virescens of a cysteine-rich molecule with exclusive antifungal activity. We have fully characterized this antifungal molecule, which has significant homology with the insect defensins, a large family of antibacterial peptides directed against Gram-positive strains. Interestingly, the novel peptide shows also similarities with the antifungal peptide drosomycin from Drosophila. Thus, Lepidoptera appear to have built their humoral immune response against bacteria on cecropins and attacins. In addition, we report that Lepidoptera have conferred antifungal properties to the well conserved structure of antibacterial insect defensins through amino acid replacements.     

石花菜和海蒿子提取物抗菌活性初步研究

采用圆形纸片法,对石花菜和海蒿子粗提取物及萃取得到的不同极性组分进行抗菌实验。结果表明,石花菜和海蒿子均有不同程度的抗菌作用,海蒿子粗取物的抗细菌活性强于抗真菌活性,而石花菜乙醇提取物抗黑曲霉活性大于抗大肠杆菌、金黄色葡萄球菌以及枯草杆菌活性,其抑菌圈可达4 mm。     

In-vitro antibacterial, antifungal and cytotoxic activity of cobalt (II), copper (II), nickel (II) and zinc (II) complexes with furanylmethyl- and thienylmethyl-dithiolenes: [1, 3-dithiole- 2-one and 1,3-dithiole-2-thione

Some antibacterial and antifungal furanylmethyl-and thienylmethyl dithiolenes and, their Co(II), Cu(II), Ni (II) and Zn (II) complexes have been synthesized, characterized and screened for their in vitro antibacterial activity against four Gram-negative; Escherichia coli, Pseudomonas aeruginosa, Salmonella typhi and Shigella flexeneri, and two Gram-positive; Bacillus subtilis and Staphylococcus aureus bacterial strains, and for in-vitro antifungal activity against Trichophyton longifusus, Candida albicans, Aspergillus flavus, Microsporum canis, Fusarium solani and Candida glaberata. All compounds showed significant antibacterial and antifungal activity. The metal complexes, however, were shown to possess better activity as compared to the simple ligands. The brine shrimp bioassay was also carried out to study their in-vitro cytotoxic properties.