Synthesis and antimicrobial activity of new 1,2,4-triazole and 1,3,4-thiadiazole derivatives

In this study, new 3-[(1(2H)-phthalazinone-2-yl(methyl/ethyl]-4-aryl-1,2,4-triazole-5-thione and 2-[[1(2H)-phthalazinone-2-yl]methyl/ethyl]-5-arylamino-1,3,4-thiadiazole derivatives were synthesized. Antimicrobial properties of the title compounds were investigated against two Gram (+) bacteria (S. aureus, B. subtilis), two Gram ( ? ) bacteria (P. aeruginosa, E. coli) and two yeast-like fungi (C. albicans and C. parapsilosis) using the broth microdilution method. Generally the compounds were found to be active against B. subtilis and the fungi. Derivatives carrying a 1,3,4-thiadiazole ring generally showed higher antimicrobial activity against B. subtilis and the fungi when compared to other synthesized compounds.     

Synthesis and antimicrobial activity of amide derivatives of polyether antibiotic-salinomycin

For the first time a direct and practical approach to the synthesis of eight amide derivatives of polyether antibiotic-salinomycin is described. The structure of allyl amide (3a) has been determined using X-ray diffraction. Salinomycin and its amide derivatives have been screened for their in vitro antimicrobial activity against the typical gram-positive cocci, gram-negative rods and yeast-like organisms, as well as against a series of clinical isolates of methicillin-resistant Staphylococcus aureus and methicillin-sensitive S. aureus. Amides of salinomycin have been found to show a wide range of activities, from inactive at 256 μg/mL to active with MIC of 2 μg/mL, comparable with salinomycin. As a result, phenyl amide (3b) was found to be the most active salinomycin derivative against gram-positive bacteria, MRSA and MSSA.     

Synthesis and antimicrobial activity of new 1,2,4-triazole and 1,3,4-thiadiazole derivatives

In this study, new 3-[(1(2H)-phthalazinone-2-yl(methyl/ethyl]-4-aryl-1,2,4-triazole-5-thione and 2-[[1(2H)-phthalazinone-2-yl]methyl/ethyl]-5-arylamino-1,3,4-thiadiazole derivatives were synthesized. Antimicrobial properties of the title compounds were investigated against two Gram (+) bacteria (S. aureus, B. subtilis), two Gram ( - ) bacteria (P. aeruginosa, E. coli) and two yeast-like fungi (C. albicans and C. parapsilosis) using the broth microdilution method. Generally the compounds were found to be active against B. subtilis and the fungi. Derivatives carrying a 1,3,4-thiadiazole ring generally showed higher antimicrobial activity against B. subtilis and the fungi when compared to other synthesized compounds.     

Synthesis of selenium-containing amino acid analogues and their biological study

Synthesis of selenium-containing amino acid analogues is described. These compounds were prepared in a concise and short synthetic route in good yields by nucleophilic substitution reaction of pyridineselenol and quinolineselenol derivatives with N-phthaloylglycyl chloride followed by hydrazinolysis. The newly synthesized compounds were screened against different strains of bacteria and fungi.     

Quantitative relationships between structure and antimicrobial activity of new “Soft” bisquaternary ammonium salts

New surface-active bisquaternary ammonium salts derived from bis-(2-dimethylaminoethyl) ester of glutaric acid are highly effective against representatives of Gram-positive, Gram-negative bacteria and yeasts. Relationships between structure, lipophilicity and antimicrobial effectiveness were demonstrated by quantitative structure-activity methodology. The nonlinear dependence of biological activity on the structure as well as lipophilicity (expressed as critical micelle concentration—CMC) was shown using Kubinyi’s bilinear model. The most effective compounds were those with the alkyl chain of 11–12 carbon atoms and with the CMC values around 0.7−1.0 mmol/L. These derivatives possessed higher antimicrobial activity particularly to Gram-negative bacteria. Part 45 of the seriesQuaternary Ammonium Salts; part 44: Brádlerová A.et al., Pharmazie, in press.     

Antimicrobial activity of two novel coumarin derivatives: 3-cyanonaphtho[1,2-(e)] pyran-2-one and 3-cyanocoumarin

The antimicrobial activity of the two novel coumarin derivatives, 3-cyanonaphthol[1,2-(e)]pyran-2-one and 3-cyanocoumarin was determined. The two novel coumarin derivatives showed specific activity against most gram-positive organisms and yeast with lower activity against most gram-negative bacteria. The MIC values of compounds showed that they are largely active against E. coli to a lesser extent against S. aureus and C. albicans.     

Production of extracellular polymers by yeast-like generaDipodascus andDipodascopsis under NaCl stress

Changes in the production and basal characteristics of extracellular polymeric compounds were analyzed in eight yeast-like fungi of the generaDipodascus andDipodascopsis in media with and without the addition of NaCl. In the presence of higher concentration of NaCl (8%) the strains produced extracellular polymers (EP) of relatively lower molar mass. Stress EP contained a higher percentage of glutamic acid, mannose and galactose than normal EP. The production of these compounds is probably part of the adaptation mechanism and extracellular protection against disbalanced growth.     

Isolation and structural characterisation of two antibacterial free fatty acids from the marine diatom, <Emphasis Type="Italic">Phaeodactylum tricornutum</Emphasis>

One solution to the global crisis of antibiotic resistance is the discovery of novel antimicrobial compounds for clinical application. Marine organisms are an attractive and, as yet, relatively untapped resource of new natural products. Cell extracts from the marine diatom, Phaeodactylum tricornutum, have antibacterial activity and the fatty acid, eicosapentaenoic acid (EPA), has been identified as one compound responsible for this activity. During the isolation of EPA, it became apparent that the extracts contained further antibacterial compounds. The present study was undertaken to isolate these additional antibacterial factors using silica column chromatography and reverse-phase high-performance liquid chromatography. Two antibacterial fractions, each containing a pure compound, were isolated and their chemical structures were investigated by mass spectrometry and nuclear magnetic resonance spectroscopy. The antibacterial compounds were identified as the monounsaturated fatty acid (9Z)-hexadecenoic acid (palmitoleic acid; C16:1 n-7) and the relatively unusual polyunsaturated fatty acid (6Z, 9Z, 12Z)-hexadecatrienoic acid (HTA; C16:3 n-4). Both are active against Gram-positive bacteria with HTA further inhibitory to the growth of the Gram-negative marine pathogen, Listonella anguillarum. Palmitoleic acid is active at micro-molar concentrations, kills bacteria rapidly, and is highly active against multidrug-resistant Staphylococcus aureus. These free fatty acids warrant further investigation as a new potential therapy for drug-resistant infections.     

Structure-Biological Activity Relationships in Alfalfa Antimycotic Saponins: The Relative Activity of Medicagenic Acid and Synthetic Derivatives Thereof Against Plant Pathogenic Fungi1

The antimycotic activity of medicagenic acid and of some synthetic derivatives thereof was tested against plant pathogenic fungi. In general they all possess antimycotic activity. Furthermore, in the case of Sclerotium rolfsii, compounds where the hydroxyl functions of the aglycon remained unchanged (medicagenic acid and its dimethyl ester) or could be enzymically released (3-0-β-D-glucoside of medicagenic acid dimethyl ester) were significantly more active than compounds where these functions were modified by acetylation or methylation. Selective 2-0-methylation of medicagenic acid and comparison of the antimycotic activity of the resulting derivative against S. rolfsii to that of other derivatives suggests that a potential free hydroxyl at position 3 is essential to antimycotic activity.     

Synthesis and in Vitro Antimicrobial Activity Screening of New 3‐Acetyl‐2,5‐disubstituted‐1,3,4‐oxadiazoline Derivatives

Thirteen new 3‐acetyl‐2,5‐disubstituted‐1,3,4‐oxadiazoline derivatives were synthesized from corresponding hydrazide‐hydrazones of isonicotinic acid in the reaction with acetic anhydride. The obtained compounds were identified with the use of spectral methods (IR, ¹H‐NMR, ¹³C‐NMR, MS). In vitro antimicrobial activity screening of synthesized compounds against a panel of bacteria and fungi revealed interesting antibacterial and antifungal activity of tested 1,3,4‐oxadiazoline derivatives, which is comparable to that of commonly used antimicrobial agents.     

Synthesis of Some New Halogenated N-Thiazolyl Substituted 2-Mercapto Benzoic Acid Amides and Their Use as Possible Fungicides

One hundred and four acid amido compounds have been prepared by condensing 2-mercapto benzoic acid and its 5-bromo, 3, 5-dibromo and 3, 5-dichloro derivatives with 2-amino-4-substituted thiazoles and their 5-halogenated derivatives via the acid chloride. All these compounds have been tested against Helminthosporium. Four of the compounds were tested for their antibacterial, antihelminthic activities and also for their hypoglycemic activity.     

Natural products and their semi-synthetic derivatives against antimicrobial-resistant human pathogenic bacteria and fungi

Human infectious diseases caused by various microbial pathogens, in general, impact a large population of individuals every year. These microbial diseases that spread quickly remain to be a big issue in various health-related domains and to withstand the negative drug impacts, the antimicrobial-resistant pathogenic microbial organisms (pathogenic bacteria and pathogenic fungi) have developed a variety of resistance processes against many antimicrobial drug classes. During the COVID-19 outbreak, there seems to be an upsurge in drug and multidrug resistant-associated pathogenic microbial species. The preponderance of existing antimicrobials isn’t completely effective, which limits their application in clinical settings. Several naturally occurring chemicals produced from bacteria, plants, animals, marine species, and other sources are now being studied for antimicrobial characteristics. These natural antimicrobial compounds extracted from different sources have been demonstrated to be effective against a variety of diseases, although plants remain the most abundant source. These compounds have shown promise in reducing the microbial diseases linked to the development of drug tolerance and resistance. This paper offers a detailed review of some of the most vital and promising natural compounds and their derivatives against various human infectious microbial organisms. The inhibitory action of different natural antimicrobial compounds, and their possible mechanism of antimicrobial action against a range of pathogenic fungal and bacterial organisms, is provided. The review will be useful in refining current antimicrobial (antifungal and antibacterial) medicines as well as establishing new treatment strategies to tackle the rising number of human bacterial and fungal-associated infections.     

Synthesis,biological activity and molecular modelling studies of shikimic acid derivatives as inhibitors of the shikimate dehydrogenase enzyme of Escherichia coli

Shikimic acid (SA) pathway is the common route used by bacteria, plants, fungi, algae, and certain Apicomplexa parasites for the biosynthesis of aromatic amino acids and other secondary metabolites. As this essential pathway is absent in mammals designing inhibitors against implied enzymes may lead to the development of antimicrobial and herbicidal agents harmless to humans. Shikimate dehydrogenase (SDH) is the fourth enzyme of the SA pathway. In this contribution, a series of SA amide derivatives were synthesised and evaluated for in vitro SDH inhibition and antibacterial activity against Escherichia coli. All tested compounds showed to be mixed type inhibitors; diamide derivatives displayed more inhibitory activity than synthesised monoamides. Among the evaluated compounds, molecules called 4a and 4b were the most active derivatives with IC₅₀ 588 and 589?µM, respectively. Molecular modelling studies suggested two different binding modes of monoamide and diamide derivatives to the SDH enzyme of E. coli.     

Synthesis of a novel class of some 1,3,4-oxadiazole derivatives as antimicrobial agents

In an effort to discover new candidates with improved antimicrobial activities we report here the synthesis and in vitro biological evaluation of various series of 2-{(3,4,5-trimethoxy phenyl-1,3,4-oxadiazolyl)-5-thio}-4-(morpholino)-6-(phenyl ureido)-s-triazine (7a-i) and 2-{(3,4,5-trimethoxy phenyl-1,3,4-oxadiazolyl)-5-thio}-4-(morpholino)-6-(phenyl thioureido)-s-triazine (8a-g). Antimicrobial properties of the title compounds were investigated against two Gram ( + ve) bacteria (S. aureus, B. subtilis), two Gram ( ? ve) bacteria (P. aeruginosa, E. coli) and yeast-like fungi (C. albicans) using the broth microdilution method.     

Structure-Activity Relationships Amongst β-Lactamase Inhibitors

Abstract

Using a variety of β-lactamases including those from Escherichia coli (TEM-1), Enterobacter cloacae P99 and Staphylococcus aureus the inhibition profiles (I₅₀ values) were determined for various groups of compounds including penicillins, penicillanic acid derivatives (sulphone and β-halo substitutions), olivanic acids and clavulanic acid derivatives including substituted ethers and amines. Some of the latter compounds had higher activity than clavulanic acid with and without preincubation of enzyme with inhibitor but they still had poor activity against the P99 enzyme. Improvements in activity against Class I cephalosporinases were obtained with some derivatives of clavulanic acid but this was usually achieved at the expense of activity against clavulanate susceptible β-lactamases.The olivanic acids had the highest activity against the widest range of β-lactamases.     

Ferulic acid and its water-soluble derivatives inhibit nitric oxide production and inducible nitric oxide synthase expression in rat primary astrocytes

We recently reported that two water-soluble derivatives of ferulic acid (1-feruloyl glycerol, 1-feruloyl diglycerol) previously developed by our group exhibited protective effects against amyloid-β–induced neurodegeneration in vitro and in vivo. In the current study, we aimed to further understand this process by examining the derivatives’ ability to suppress abnormal activation of astrocytes, the key event of neurodegeneration. We investigated the effects of ferulic acid (FA) derivatives on nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) expression in rat primary astrocytes. The results showed that these compounds inhibited NO production and iNOS expression in a concentration-dependent manner and that the mechanism underlying these effects was the suppression of the nuclear factor-κB pathway. This evidence suggests that FA and its derivatives may be effective neuroprotective agents and could be useful in the treatment of neurodegenerative diseases, such as Alzheimer’s disease and Parkinson’s disease.     

Methanopterin and methanogenic bacteria

Methanogenic bacteria comprise a selected group of microorganisms that derive their energy for growth from the hydrogen-dependent reduction of CO2 to methane or the disproportionation of reduced one-carbon compounds and acetate to CO2 and methane. In the reduction and oxidation steps at the formyl, hydroxymethyl and methyl level the one-carbon unit remains bound to the reduced form of methanopterin, a pterin derivative typical of methanogenic bacteria. In addition, the reduced methanopterin, 5,6,7,8-tetrahydromethanopterin, is involved in a number of anabolic reactions. Methanopterin is structurally and functionally the counterpart of folic acid found in other organisms. In this review the occurrence and properties of methanopterin and its derivatives, as well as the biosynthesis and the role in the different catabolic and anabolic reactions are discussed against the background of folic acid biochemistry.     

Antimicrobial and antiadhesive properties of a biosurfactant isolated from Lactobacillus paracasei ssp. paracasei A20

Aims: The aim of this study was to determine the antimicrobial and antiadhesive properties of a biosurfactant isolated from Lactobacillus paracasei ssp. paracasei A20 against several micro‐organisms, including Gram‐positive and Gram‐negative bacteria, yeasts and filamentous fungi. Methods and Results: Antimicrobial and antiadhesive activities were determined using the microdilution method in 96‐well culture plates. The biosurfactant showed antimicrobial activity against all the micro‐organisms assayed, and for twelve of the eighteen micro‐organisms (including the pathogenic Candida albicans, Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus agalactiae), the minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) were achieved for biosurfactant concentrations between 25 and 50 mg ml^?1. Furthermore, the biosurfactant showed antiadhesive activity against most of the micro‐organisms evaluated. Conclusions: As far as we know, this is the first compilation of data on antimicrobial and antiadhesive activities of biosurfactants obtained from lactobacilli against such a broad group of micro‐organisms. Although the antiadhesive activity of biosurfactants isolated from lactic acid bacteria has been widely reported, their antimicrobial activity is quite unusual and has been described only in a few strains. Significance and Impact of the Study: The results obtained in this study regarding the antimicrobial and antiadhesive properties of this biosurfactant opens future prospects for its use against micro‐organisms responsible for diseases and infections in the urinary, vaginal and gastrointestinal tracts, as well as in the skin, making it a suitable alternative to conventional antibiotics.     

Evaluation of new antimicrobial agents on Bacillus spp. strains: docking affinity and in vitro inhibition of glutamate-racemase

Three glutamic acid derivatives, two boron-containing and one imide-containing compound, were synthesized and tested for antimicrobial activity targeting glutamate-racemase. Antimicrobial effect was evaluated over Bacillus spp. Docking analysis shown that the test compounds bind near the active site of racemase isoforms, suggesting an allosteric effect. The boron derivatives had greater affinity than the imide derivative. In vitro assays shown good antimicrobial activity for the boron-containing compounds, and no effectiveness for the imide-containing compounds. The minimum inhibitory concentration of tetracycline, used as standard, was lower than that of the boron-containing derivatives. However, it seems that the boron-containing derivatives are more selective for bacteria. Experimental evidence suggests that the boron-containing derivatives act by inhibiting the racemase enzyme. Therefore, these test compounds probably impede the formation of the bacterial cell wall. Thus, the boron-containing glutamic acid derivatives should certainly be of interest for future studies as antimicrobial agents for Bacillus spp.     

Derivatives of Holomycin and Cyclopropaneacetic Acid from Streptomyces sp. DT‐A37

On the basis of the one strain–many compounds strategy, five compounds including two new holomycin derivatives 2 – 3 , two new cyclopropaneacetic acid derivatives 4 – 5 , together with one known compound holomycin ( 1 ) were isolated from a marine‐derived bacterium Streptomyces sp. DT‐A37. Their structures were elucidated using NMR and HR‐ESI‐MS analyses. All these compounds were evaluated for their antimicrobial activity, cytotoxic activity, and inhibitory activity against BRD4 protein. Compound 1 exhibited potent cytotoxicity against H1975 cells with IC₅₀ value of 1 μm , and its minimal inhibitory concentration values against Escherichia coli and Staphylococcus aureus were both 64 μm .