scholarly journals Improving the Cellular Selectivity of a Membrane-Disrupting Antimicrobial Agent by Monomer Control and by Taming

Molecules ◽  
2021 ◽  
Vol 26 (2) ◽  
pp. 374
Author(s):  
Steven L. Regen
Keyword(s):  
Amphotericin B ◽  
Blood Cells ◽  
World Wide ◽  
Antimicrobial Agents ◽  
Monomer Concentration ◽  
Model Systems ◽  
Membrane Disruption ◽  
Triton X ◽  
Derivatives Of ◽  
High Antifungal Activity

Antimicrobial resistance represents a significant world-wide health threat that is looming. To meet this challenge, new classes of antimicrobial agents and the redesign of existing ones will be required. This review summarizes some of the studies that have been carried out in my own laboratories involving membrane-disrupting agents. A major discovery that we made, using a Triton X-100 as a prototypical membrane-disrupting molecule and cholesterol-rich liposomes as model systems, was that membrane disruption can occur by two distinct processes, depending on the state of aggregation of the attacking agent. Specifically, we found that monomers induced leakage, while attack by aggregates resulted in a catastrophic rupture of the membrane. This discovery led us to design of a series of derivatives of the clinically important antifungal agent, Amphotericin B, where we demonstrated the feasibility of separating antifungal from hemolytic activity by decreasing the molecule’s tendency to aggregate, i.e., by controlling its monomer concentration. Using an entirely different approach (i.e., a “taming” strategy), we found that by covalently attaching one or more facial amphiphiles (“floats”) to Amphotericin B, its aggregate forms were much less active in lysing red blood cells while maintaining high antifungal activity. The possibility of applying such “monomer control” and “taming” strategies to other membrane-disrupting antimicrobial agents is briefly discussed.

scholarly journals Synthesis and Bioevaluation of 5-Chloro-4-(1,3-Oxazol-5-yl)-1Н-Pyrrole-3-Carboxyamides as Antimicrobial Agents

2020 ◽  
Vol 11 (3) ◽  
pp. 10595-10606
Keyword(s):  
Antimicrobial Agents ◽  
Ester Group ◽  
Alkyl Aryl ◽  
Design And Synthesis ◽  
Consecutive Reactions ◽  
Efficient Construction ◽  
Further Development ◽  
Hydrolysis Of ◽  
Derivatives Of ◽  
High Antifungal Activity

This investigation deals with the design and synthesis of new derivatives of pyrrole consisting of modifying atoms of chlorine, amide, and 1,3-oxazole fragments. These compounds can be interesting in the context of research of new antimicrobial agents. Ethyl 5-chloro-4-formyl-1H-pyrrole-3-carboxylates were used as a key substrate for further transformation into target compounds. This process was realized as a direct transformation of an aldehyde fragment into a 1,3-oxazole cycle by van Leusen’s reaction followed by hydrolysis of an ester group, which finally converted a reactant into the corresponding pyrrole-3-carboxylic acid. This acid has been found to be an efficient construction block for the further development of antimicrobial agents. The preparative potential of these compounds has been verified by way of their transformation into a series of carbamides through consecutive reactions with thionyl chloride and alkyl-, aryl, and heterylamines under mild reaction conditions. According to bio screening results, the following two compounds have been chosen as those exhibiting a high anti-staphylococcus activity: 1-butyl-5-chloro-2-methyl-4-(1,3-oxazol-5-yl)-N-[(1,3-thiazol-2-yl]-1H-pyrrole-3-carboxamide and 1-butyl-5-chloro-N-[(3-dimethylaminosulfonyl)phenyl]-2-methyl-4-(1,3-oxazol-5-yl)-1H-pyrrole-3-carboxamide (МІС=7.8 µg/ml), while another one – 5-сhloro-N-(4-chlorophenyl)-4-(1,3-oxazol-5-yl)-2-phenyl-1-propyl-1H-pyrrole-3-carboxamide was selected as a compound exhibiting high antifungal activity (МІС=7.8 µg/ml) against the reference strains Candida albiсans АТСС 885/653 and Aspergillus niger K9.

Spectrophotometric study of the complexation equilibria of cadmium ions with 5-bromo and 5-chloro derivatives of 2-(2-pyridylazo)-5-diethylaminophenol (BrPADAP, ClPADAP)

1983 ◽  
Vol 48 (1) ◽  
pp. 52-59 ◽  
Author(s):  
Vlastimil Kubáň ◽  
Miroslav Macka
Keyword(s):  
Equilibrium Constants ◽  
Spectrophotometric Study ◽  
Graphical Analysis ◽  
Optimal Conditions ◽  
Cadmium Ions ◽  
Brij 35 ◽  
Ethanol Medium ◽  
Triton X ◽  
Derivatives Of

The composition, optical characteristics, molar absorption coefficients and equilibrium constants of the reactions of formation of the ML and ML2 complexes of both reagents with cadmium(II) ions were determined by graphical analysis and numerical interpretation of the absorbance-pH curves by the modified SQUAD-G program. Optimal conditions were proposed for the spectrophotometric determination of Cd in 10% v/v ethanol medium in the presence of 0.1% w/v Triton X-100 or 1% w/v Brij 35. BrPADAP and ClPADAP are the most sensitive spectrophotometric reagents for the determination of cadmium(II) ions (ε = 1.28-1.44 . 105 mmol-1 cm2 at 560 nm and pH 8.0-9.5) with a high colour contrast in the reaction (Δλmax ~117 nm) and a selectivity similar to that of other N-heterocyclic azodyes (PAR, PAN, etc.).

Spectrophotometric study of the acid-base and optical properties of the 5-bromo and 5-chloro derivatives of 2-(2-pyridylazo)-5-(diethylamino)phenol (BrPADAP, ClPADAP) and their complexation equilibria with zinc(II) ions

1982 ◽  
Vol 47 (10) ◽  
pp. 2676-2691 ◽  
Author(s):  
Miroslav Macka ◽  
Vlastimil Kubáň
Keyword(s):  
Equilibrium Constants ◽  
Spectrophotometric Study ◽  
Graphical Analysis ◽  
Alkaline Media ◽  
Acid Base ◽  
Ethanol Medium ◽  
Triton X ◽  
Mixed Water ◽  
Derivatives Of

The optical and acid-base characteristics of BrPADAP and ClPADAP were studied in mixed water-ethanol and water-DMF media and in 10% ethanol medium in the presence of cationic, anionic and nonionic tensides. The composition, optical characteristics, molar absorption coefficients and equilibrium constants of the ML and ML2 complexes with zinc(II) ions were found by graphical analysis and numerical interpretation of the absorbance curves by the modified SQUAD-G program. Optimal conditions were found for the spectrophotometric determination of Zn(II) in the presence of 0.1% Triton X-100 or 1% Brij 35 in alkaline media with pH = 6.5-10. BrPADAP and ClPADAP are the most sensitive reagents (ε = 1.3-1.6 . 105 mmol-1 cm2 at 557 and 560 nm, respectively) for the determination of zinc with high colour contrast of the reaction (Δλ = 104 nm) and selectivity similar to that for the other N-heterocyclic azodyes (PAN, PAR, etc.).

scholarly journals Black and white teas as potential agents to combine with amphotericin B and protect red blood cells from amphotericin B-mediated toxicity

2018 ◽  
Vol 78 (4) ◽  
pp. 673-678 ◽  
Author(s):  
V. M. Oliveira ◽  
N. M. Khalil ◽  
E. Carraro
Keyword(s):  
Side Effects ◽  
Red Blood Cells ◽  
Amphotericin B ◽  
Blood Cells ◽  
Fungal Infections ◽  
Black Tea ◽  
Additive Effects ◽  
Antifungal Effect ◽  
Black And White ◽  
Fungicidal Substance

Abstract Amphotericin B is a fungicidal substance that is treatment of choice for most systemic fungal infections affecting immunocompromised patients. However, severe side effects have limited the utility of this drug. The aim of this study was to evaluate the antifungal effect of the combination of amphotericin B with black tea or white tea and protective of citotoxic effect. The present study shows that white and black teas have additive effects with amphotericin B against some species Candida. In addition, the combination of white and black tea with amphotericin B may reduce the toxicity of amphotericin B to red blood cells. Our results suggest that white and black tea is a potential agent to combine with amphotericin for antifungal efficacy and to reduce the amphotericin dose to lessen side effects.

scholarly journals SYNTHESIS AND ANTIMICROBIAL EVALUATION OF QUINAZOLINONE PEPTIDE DERIVATIVES

2017 ◽  
Vol 10 (16) ◽  
pp. 7 ◽  
Author(s):  
Bhupinder Kapoor ◽  
Arshid Nabi ◽  
Reena Gupta ◽  
Mukta Gupta
Keyword(s):  
Antibacterial Activity ◽  
Amino Acid ◽  
Antimicrobial Agents ◽  
Methyl Esters ◽  
Standard Drug ◽  
Amino Acid Peptide ◽  
Chemical Structures ◽  
1H Nuclear Magnetic Resonance ◽  
Peptide Derivatives ◽  
Derivatives Of

  Objective: The increased microbial resistance against commercially available drugs initiated the development of novel and safe antimicrobial agents in last few decades. In this view, a series of amino acid/dipeptide derivatives of quinazolin-3(4H)-one was synthesized and was evaluated for their antimicrobial potential.Method: Synthesis of amino acid/peptide derivatives were carried out by coupling 5-(2-(2-chlorophenyl)-4-oxoquinazolin-3(4H)-yl)-2-hydroxy benzoic acid with amino acid/dipeptide methyl esters in the presence of dicyclohexylcarbodiimide and N-methylmorpholine. The chemical structures of synthesized compounds were characterized by 1H nuclear magnetic resonance and infrared spectroscopy and were screened for antibacterial activity by disc diffusion method.Results: All the synthesized derivatives exhibited moderate to significant antibacterial activity against both Gram-positive and Gram-negative bacteria. The potency of compound 5d was comparable to standard drug ciprofloxacin in all the strains of bacteria used. The compound 5a was found to be more active against Streptococcus pyogenes and Staphylococcus aureus while compound 5c against Pseudomonas aeruginosa and Escherichia coli. Conclusion: Peptide derivatives of quinazolinone are promising antimicrobial agent and can be used for the synthesis of other novel compounds.

scholarly journals Microbial Transformations of Isophorone by Alternaria alternata and Neurospora crassa

2013 ◽  
Vol 8 (1) ◽  
pp. 1934578X1300800 ◽  
Author(s):  
Ismail Kiran ◽  
Özge Özşen ◽  
Turgay Çelik ◽  
Semra İlhan ◽  
Bükay Yenice Gürsu ◽  
...  
Keyword(s):  
Neurospora Crassa ◽  
Alternaria Alternata ◽  
Antimicrobial Agents ◽  
Antimicrobial Activities ◽  
Anti Oxidant ◽  
Agar Dilution ◽  
Important Field ◽  
Pharmacology And Toxicology ◽  
Derivatives Of

Isophorone (3,5,5-trimethyl-2-cyclohexen-1-one), a monoterpene, and the structurally related 1,8-cineole and camphor, have demonstrated a protective effect against cancer, biological activity against a variety of microorganisms, and anti-oxidant properties. The derivatization of isophorone is, therefore, an important field of xenobiochemistry, pharmacology and toxicology. The aim of this study was to obtain derivatives of isophorone through microbial biotransformation and evaluate the biotransformation metabolites as potential antimicrobial agents. Incubation of isophorone with the fungi Alternaria alternata and Neurospora crassa afforded 4α-hydroxy- and 7-hydroxy-isophorone as transformation metabolites. The antimicrobial activities of isophorone and the metabolites were evaluated in vitro both by using agar dilution and microdilution methods. However, no significant antibacterial activity was observed when compared with those of standard substances.

THE PRODUCTION OF PURPURA BY DERIVATIVES OF PNEUMOCOCCUS

1926 ◽  
Vol 43 (1) ◽  
pp. 111-106
Author(s):  
Hobart A. Reimann ◽  
Louis A. Julianelle
Keyword(s):  
Red Blood Cells ◽  
Hemolytic Activity ◽  
Blood Cells ◽  
Blood Platelets ◽  
White Blood Cells ◽  
Red Cells ◽  
Severe Anemia ◽  
Marked Diminution ◽  
Derivatives Of

A study has been made of the variation in number of the blood platelets, and the red and white blood cells of white mice injected with pneumococcus extract. The blood platelets were greatly diminished after the injection, the greatest decrease usually occurring after 24 hours. Purpuric lesions usually developed when the number of blood platelets became less than 500,000 per c.mm. Regeneration of the platelets was accomplished by the 4th to the 9th day but there was an overregeneration and the return to normal did not take place until 2 weeks had elapsed. The red cells were also greatly reduced in number, but the rate of their destruction and regeneration was somewhat slower than that of the platelets. The leucocytes were slightly if at all influenced by the pneumococcus extract. Pneumococcus extracts were shown to be thrombolytic and hemolytic. Heat destroyed the activity of both the lysins in vitro. Heated extract produced purpura in mice but did not cause a severe anemia. Extracts adsorbed with either blood platelets or red blood cells showed a marked diminution in their thrombolytic and hemolytic activity in vitro. Such extracts, however, produced purpura as well as severe anemia and thrombopenia in mice.

scholarly journals Preparation and Hydro-Lipophilic Properties of Selected Novel Chlorinated and Brominated N-Arylcinnamamides

Proceedings ◽  
2019 ◽  
Vol 41 (1) ◽  
pp. 11
Author(s):  
Tomas Strharsky ◽  
Timotej Jankech ◽  
Jiri Kos ◽  
Kristina Maricakova ◽  
Andrea Pramukova ◽  
...  
Keyword(s):  
High Performance ◽  
Chemical Structure ◽  
Antimicrobial Agents ◽  
Reversed Phase ◽  
Log P ◽  
Organic Modifier ◽  
Chromatography Method ◽  
P Values ◽  
Liquid Chromatography Method ◽  
Derivatives Of

A series of six di- and tri-halogenated N-arylcinnamanilides designed as anti-inflammatory and antimicrobial agents was prepared and characterized. Since it is known that lipophilicity significantly influences the biological activity of compounds, the hydro-lipophilic properties of these di- and tri-substituted N-arylcinnamanilides were investigated in the study. All the discussed derivatives of cinnamic acid were analyzed using the reversed-phase high performance liquid chromatography method to measure lipophilicity. The procedure was performed under isocratic conditions with methanol as an organic modifier in the mobile phase using an end-capped non-polar C18 stationary reversed-phase column. In the present study, the correlations between the logarithm of the capacity factor k and log P/Clog P values calculated in various ways as well as the relationships between the lipophilicity and the chemical structure of the studied compounds are discussed.

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