Ethylzingerone, a Novel Compound with Antifungal Activity

Preservatives increase the shelf life of cosmetic products by preventing growth of contaminating microbes, including bacteria and fungi. In recent years, the Scientific Committee on Consumer Safety (SCCS) has recommended the ban or restricted use of a number of preservatives due to safety concerns. Here, we characterize the antifungal activity of Ethylzingerone (Hydroxyethoxyphenyl butanone, HEPB), an SCCS-approved new preservative for use in rinse-off, oral care and leave-on cosmetic products. We show that HEPB significantly inhibits growth of Candida albicans, Candida glabrata and Saccharomyces cerevisiae, acting fungicidally against C. albicans. Using transcript profiling experiments, we found that the C. albicans transcriptome responded to HEPB exposure by increasing the expression of genes involved in amino acid biosynthesis, while activating pathways involved in chemical detoxification/oxidative stress response. Comparative analyses revealed that C. albicans phenotypic and transcriptomic responses to HEPB treatment were distinguishable from those of two widely used preservatives, triclosan and methylparaben. Chemogenomic analyses, using a barcoded S. cerevisiae non-essential mutant library, revealed that HEPB antifungal activity strongly interfered with the biosynthesis of aromatic amino acids. The trp1Δ mutants in S. cerevisiae and C. albicans were particularly sensitive to HEPB treatment, a phenotype rescued by exogenous addition of tryptophan to the growth medium, providing a direct link between HEPB mode-of-action and tryptophan availability. Collectively, our study sheds light on the antifungal activity of HEPB, a new molecule with safe properties for use as a preservative in cosmetics industry, and exemplifies the powerful use of functional genomics to illuminate the mode-of-action of antimicrobial agents.

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Risk Assessment of Cosmetic Preservatives Using QSAR

International Journal of Quantitative Structure-Property Relationships ◽

10.4018/ijqspr.2020010103 ◽

2020 ◽

Vol 5 (1) ◽

pp. 44-62

Author(s):

Monika Bhardwaj ◽

Neeraj Masand ◽

Jagannath Sahoo ◽

Vaishali M. Patil

Keyword(s):

Microbial Contamination ◽

Antimicrobial Agents ◽

Quantitative Structure Activity Relationship ◽

Toxicity Assessment ◽

Cosmetic Products ◽

Toxicity Prediction ◽

Safety And Efficacy ◽

Regulatory Aspects ◽

Structure Activity ◽

Consumer Safety

Cosmetic manufacturers need to demonstrate the safety and efficacy of the products against microbial contamination to assure consumer safety and to improve shelf-life. The preservation strategies include chemical, physical, or physiological strategies. The most common is the use of antimicrobial agents. The toxicity assessment of preservatives used in cosmetic products is essential. It can be done by computational methods such as quantitative structure-activity relationship (QSAR) using several software such as ADME-Tox, TOPKAT, Dragon, T.E.S.T., and ECOSAR. The present manuscript elaborates a detailed view on cosmetic preservatives, regulatory aspects and application of computational strategies for toxicity prediction.

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Novel Thiazole-Based Thiazolidinones as Potent Anti-infective Agents: In silico PASS and Toxicity Prediction, Synthesis, Biological Evaluation and Molecular Modelling

Combinatorial Chemistry & High Throughput Screening ◽

10.2174/1386207323666200127115238 ◽

2020 ◽

Vol 23 (2) ◽

pp. 126-140 ◽

Cited By ~ 1

Author(s):

Christophe Tratrat

Keyword(s):

In Silico ◽

Antimicrobial Agents ◽

Target Identification ◽

Biological Evaluation ◽

Microbial Infection ◽

Toxicity Prediction ◽

Discovery Studio ◽

Bacteria And Fungi ◽

Multiple Drugs ◽

Antibacterial And Antifungal

Aims and Objective: The infectious disease treatment remains a challenging concern owing to the increasing number of pathogenic microorganisms associated with resistance to multiple drugs. A promising approach for combating microbial infection is to combine two or more known bioactive heterocyclic pharmacophores in one molecular platform. Herein, the synthesis and biological evaluation of novel thiazole-thiazolidinone hybrids as potential antimicrobial agents were dissimilated. Materials and Methods: The preparation of the substituted 5-benzylidene-2-thiazolyimino-4- thiazolidinones was achieved in three steps from 2-amino-5-methylthiazoline. All the compounds have been screened in PASS antibacterial activity prediction and in a panel of bacteria and fungi strains. Minimum inhibitory concentration and minimum bacterial concentration were both determined by microdilution assays. Molecular modeling was conducted using Accelrys Discovery Studio 4.0 client. ToxPredict (OPEN TOX) and ProTox were used to estimate the toxicity of the title compounds. Results: PASS prediction revealed the potentiality antibacterial property of the designed thiazolethiazolidinone hybrids. All tested compounds were found to kill and to inhibit the growth of a vast variety of bacteria and fungi, and were more potent than the commercial drugs, streptomycin, ampicillin, bifomazole and ketoconazole. Further, in silico study was carried out for prospective molecular target identification and revealed favorable interaction with the target enzymes E. coli MurB and CYP51B of Aspergillus fumigatus. Toxicity prediction revealed that none of the active compounds was found toxic. Conclusion: Substituted 5-benzylidene-2-thiazolyimino-4-thiazolidinones, endowing remarkable antibacterial and antifungal properties, were identified as a novel class of antimicrobial agents and may find a potential therapeutic use to eradicate infectious diseases.

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Antifungal Activity, Mode of Action, Docking Prediction and Anti-biofilm Effects of (+)-β-pinene Enantiomers against Candida spp.

Current Topics in Medicinal Chemistry ◽

10.2174/1568026618666181115103104 ◽

2019 ◽

Vol 18 (29) ◽

pp. 2481-2490 ◽

Cited By ~ 6

Author(s):

Ana Cláudia de Macêdo Andrade ◽

Pedro Luiz Rosalen ◽

Irlan Almeida Freires ◽

Luciana Scotti ◽

Marcus Tulius Scotti ◽

...

Keyword(s):

Antifungal Activity ◽

Mode Of Action ◽

Candida Spp ◽

Activity Mode

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Copper-catalyzed Convenient Synthesis and SAR Studies of Substituted-1,2,3-triazole as Antimicrobial Agents

Letters in Drug Design & Discovery ◽

10.2174/1570180815666180326153322 ◽

2018 ◽

Vol 16 (1) ◽

pp. 3-10

Author(s):

Aniket P. Sarkate ◽

Kshipra S. Karnik ◽

Pravin S. Wakte ◽

Ajinkya P. Sarkate ◽

Ashwini V. Izankar ◽

...

Keyword(s):

Antimicrobial Activity ◽

Antifungal Activity ◽

Antimicrobial Agents ◽

Cycloaddition Reaction ◽

Dipolar Cycloaddition ◽

One Pot ◽

Triazole Derivatives ◽

Sar Studies ◽

Convenient Synthesis ◽

Antibacterial And Antifungal

Background:A novel copper-catalyzed synthesis of substituted-1,2,3-triazole derivatives has been developed and performed by Huisgen 1,3-dipolar cycloaddition reaction of azides with alkynes. The reaction is one-pot multicomponent.Objective:We state the advancement and execution of a methodology allowing for the synthesis of some new substituted 1,2,3-triazole analogues with antimicrobial activity.Methods:A series of triazole derivatives was synthesized by Huisgen 1,3-dipolar cycloaddition reaction of azides with alkynes. The structures of the synthesized compounds were elucidated and confirmed by 1H NMR, IR, MS and elemental analysis. All the synthesized compounds were tested for their antimicrobial activity against a series of strains of Bacillus subtilis, Staphylococcus aureus and Escherichia coli for antibacterial activity and against the strains of Candida albicans, Aspergillus flavus and Aspergillus nigar for antifungal activity, respectively.Results and Conclusion:From the antimicrobial data, it was observed that all the newly synthesized compounds showed good to moderate level of antibacterial and antifungal activity.

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The newly synthesized thiazole derivatives as potential antifungal compounds against Candida albicans

Applied Microbiology and Biotechnology ◽

10.1007/s00253-021-11477-7 ◽

2021 ◽

Author(s):

Anna Biernasiuk ◽

Anna Berecka-Rycerz ◽

Anna Gumieniczek ◽

Maria Malm ◽

Krzysztof Z. Łączkowski ◽

...

Keyword(s):

Cell Wall ◽

Candida Albicans ◽

Antifungal Activity ◽

Cell Membrane ◽

Mode Of Action ◽

Thiazole Derivatives ◽

Fungal Cell ◽

Erythrocyte Lysis ◽

Low Cytotoxicity ◽

High Antifungal Activity

Abstract Recently, the occurrence of candidiasis has increased dramatically, especially in immunocompromised patients. Additionally, their treatment is often ineffective due to the resistance of yeasts to antimycotics. Therefore, there is a need to search for new antifungals. A series of nine newly synthesized thiazole derivatives containing the cyclopropane system, showing promising activity against Candida spp., has been further investigated. We decided to verify their antifungal activity towards clinical Candida albicans isolated from the oral cavity of patients with hematological malignancies and investigate the mode of action on fungal cell, the effect of combination with the selected antimycotics, toxicity to erythrocytes, and lipophilicity. These studies were performed by the broth microdilution method, test with sorbitol and ergosterol, checkerboard technique, erythrocyte lysis assay, and reversed phase thin-layer chromatography, respectively. All derivatives showed very strong activity (similar and even higher than nystatin) against all C. albicans isolates with minimal inhibitory concentration (MIC) = 0.008–7.81 µg/mL Their mechanism of action may be related to action within the fungal cell wall structure and/or within the cell membrane. The interactions between the derivatives and the selected antimycotics (nystatin, chlorhexidine, and thymol) showed additive effect only in the case of combination some of them and thymol. The erythrocyte lysis assay confirmed the low cytotoxicity of these compounds as compared to nystatin. The high lipophilicity of the derivatives was related with their high antifungal activity. The present studies confirm that the studied thiazole derivatives containing the cyclopropane system appear to be a very promising group of compounds in treatment of infections caused by C. albicans. However, this requires further studies in vivo. Key points • The newly thiazoles showed high antifungal activity and some of them — additive effect in combination with thymol. • Their mode of action may be related with the influence on the structure of the fungal cell wall and/or the cell membrane. • The low cytotoxicity against erythrocytes and high lipophilicity of these derivatives are their additional good properties. Graphical abstract

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Evaluation of Antifungal Activity by Mixed Oxide Metallic Nanocomposite against Candida spp.

Processes ◽

10.3390/pr9050773 ◽

2021 ◽

Vol 9 (5) ◽

pp. 773

Author(s):

Ayodeji Precious Ayanwale ◽

Brenda Lizbeth Estrada-Capetillo ◽

Simón Yobanny Reyes-López

Keyword(s):

Antifungal Activity ◽

Antimicrobial Agents ◽

Mononuclear Cells ◽

Promising Result ◽

Sol Gel ◽

Group Analysis ◽

Candida Spp ◽

Human Mononuclear Cells ◽

Viability Study ◽

High Doses

High doses of antimicrobial agents are a huge threat due to the increasing number of pathogenic organisms that are becoming resistant to antimicrobial agents. This resistance has led to a search for alternatives. Therefore, this study presents the synthesis and characterization of ZrO2-Ag2O nanoparticles (NPs) by sol-gel. The NPs were analyzed by dynamic light scattering (DLS), UV-visible (UV-vis), Raman and scanning electron microscopy (SEM). The NPs were later evaluated for their antifungal effects against Candidaalbicans, Candida dubliniensis, Candida glabrata, and Candida tropicalis, using disc diffusion and microdilution methods, followed by the viability study. The DLS showed sizes for ZrO2 76 nm, Ag2O 50 nm, and ZrO2-Ag2O samples between 14 and 42 nm. UV-vis shows an absorption peak at 300 nm for ZrO2 and a broadband for Ag2O NPs. Raman spectra were consistent with factor group analysis predictions. SEM showed spherically shaped NPs. The antifungal activity result suggested that ZrO2-Ag2O NPs were effective against Candida spp. From the viability study, there was no significance difference in viability as a function of time and concentration on human mononuclear cells. This promising result can contribute toward the development of alternative therapies to treat fungal diseases in humans.

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Green synthesis of silver nanoparticles: biomolecule-nanoparticle organizations targeting antimicrobial activity

RSC Advances ◽

10.1039/c8ra08982e ◽

2019 ◽

Vol 9 (5) ◽

pp. 2673-2702 ◽

Cited By ~ 139

Author(s):

Anupam Roy ◽

Onur Bulut ◽

Sudip Some ◽

Amit Kumar Mandal ◽

M. Deniz Yilmaz

Keyword(s):

Antimicrobial Activity ◽

Silver Nanoparticles ◽

Green Synthesis ◽

Mode Of Action ◽

Antimicrobial Agents ◽

Recent Advances

In this review, we discuss the recent advances in green synthesis of silver nanoparticles, their application as antimicrobial agents and mechanism of antimicrobial mode of action.

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An In Vitro Study on the Antimicrobial Properties of Essential Oil Modified Resin Composite against Oral Pathogens

Materials ◽

10.3390/ma13194383 ◽

2020 ◽

Vol 13 (19) ◽

pp. 4383

Author(s):

Barbara Lapinska ◽

Aleksandra Szram ◽

Beata Zarzycka ◽

Janina Grzegorczyk ◽

Louis Hardan ◽

...

Keyword(s):

Antimicrobial Activity ◽

Antibacterial Activity ◽

Antifungal Activity ◽

Antimicrobial Agents ◽

Resin Composite ◽

Antimicrobial Properties ◽

In Vitro Study ◽

Diffusion Method ◽

Oral Pathogens

Modifying the composition of dental restorative materials with antimicrobial agents might induce their antibacterial potential against cariogenic bacteria, e.g., S.mutans and L.acidophilus, as well as antifungal effect on C.albicans that are major oral pathogens. Essential oils (EOs) are widely known for antimicrobial activity and are successfully used in dental industry. The study aimed at evaluating antibacterial and antifungal activity of EOs and composite resin material (CR) modified with EO against oral pathogens. Ten EOs (i.e., anise, cinnamon, citronella, clove, geranium, lavender, limette, mint, rosemary thyme) were tested using agar diffusion method. Cinnamon and thyme EOs showed significantly highest antibacterial activity against S.mutans and L.acidophilus among all tested EOs. Anise and limette EOs showed no antibacterial activity against S.mutans. All tested EOs exhibited antifungal activity against C.albicans, whereas cinnamon EO showed significantly highest and limette EO significantly lowest activity. Next, 1, 2 or 5 µL of cinnamon EO was introduced into 2 g of CR and microbiologically tested. The modified CR showed higher antimicrobial activity in comparison to unmodified one. CR containing 2 µL of EO showed the best antimicrobial properties against S.mutans and C.albicans, while CR modified with 1 µL of EO showed the best antimicrobial properties against L.acidophilus.

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Synthesis and Evaluation of Schiff Bases of 4-Amino-5-(chlorine substituted phenyl)-4H-1,2,4-triazole-3-thione as Antimicrobial Agents

Journal of Nepal Chemical Society ◽

10.3126/jncs.v41i1.30373 ◽

2020 ◽

Vol 41 (1) ◽

pp. 26-35

Author(s):

Kishor Devkota ◽

Govinda Pathak ◽

Bhushan Shakya

Keyword(s):

Schiff Base ◽

Schiff Bases ◽

Antimicrobial Agents ◽

Triazole Ring ◽

Antimicrobial Activities ◽

Biologically Active ◽

Spectral Techniques ◽

Schiff Base Derivatives ◽

Bacteria And Fungi ◽

Different Strains

Triazole ring system has attracted a continuously growing interest of synthetic organic chemists and those dealing with the medicinal compounds due to its versatile potential to interact with biological systems. Schiff bases are also considered as one of the most biologically active compounds. The aim of the present study was to synthesize new Schiff bases bearing triazole nucleus and to assess their antimicrobial activities. Four new Schiff base derivatives of 1,2,4-triazole-3-thione were synthesized by combining two different pharmacophores viz. triazole nucleus and Schiff base moiety and were characterized by spectral techniques (UV, FT-IR, and NMR). The Schiff bases were evaluated for antibacterial (Staphylococcus aureus, Escherichia coli, and Klebsiella pneumoniae) and antifungal (Candida albicans) activities. The synthesized compounds exhibited good to moderate activities against different strains of bacteria and fungi tested.

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