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Special Issue "Frontiers in Antimicrobial Drug Discovery and Design"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: closed (10 April 2017)

Special Issue Editors

Guest Editor
Prof. Dr. Daniela Barlocco

Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Mangiagalli 25, 20133 Milano, Italy
Website | E-Mail
Interests: protein–protein interaction inhibitors; enzyme inhibitors; multitarget drugs; anticancer agents
Assistant Guest Editor
Dr. Fiorella Meneghetti

Department of Pharmaceutical Sciences (DISFARM), University of Milan, Milano, Italy
Website | E-Mail
Interests: diffraction techniques; solid state analysis; structure elucidation; conformation of bioactive compounds

Special Issue Information

Dear Colleagues,

Infectious diseases still account for a substantial proportion of deaths worldwide. The plague of antimicrobial resistance represents an alarming signal for both human and animal healthcare.

There is of great interest in the opportunities and challenges associated with tackling infectious diseases for developing effective and possibly cheap antimicrobial agents endowed with new mechanisms of action.

The discovery of new antimicrobials as well as the expansion of existing antibiotics utility would be crucial to fight the ever-increasing antimicrobial resistance of “superbugs”, pathogenic fungi, viruses, and parasites.

This Special Issue aims to highlight the recent medicinal chemistry research on new antimicrobial drugs.

Prof. Dr. Daniela Barlocco
Dr. Fiorella Meneghetti
Guest Editors

Manuscript Submission Information

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Keywords

  • small molecules
  • peptides
  • peptidomimetics
  • bacterial infections
  • fungi
  • viruses
  • parasites
  • drug design
  • computational tools
  • biology assays
  • resistance mechanisms

Published Papers (14 papers)

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Editorial

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Open AccessFeature PaperEditorial Special Issue: Frontiers in Antimicrobial Drug Discovery and Design
Molecules 2017, 22(7), 1127; doi:10.3390/molecules22071127
Received: 4 July 2017 / Accepted: 4 July 2017 / Published: 6 July 2017
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(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)

Research

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Open AccessArticle Discovery of Indeno[1,2-c]quinoline Derivatives as Potent Dual Antituberculosis and Anti-Inflammatory Agents
Molecules 2017, 22(6), 1001; doi:10.3390/molecules22061001
Received: 17 May 2017 / Revised: 9 June 2017 / Accepted: 12 June 2017 / Published: 16 June 2017
Cited by 2 | PDF Full-text (2274 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
A series of indeno[1,2-c]quinoline derivatives were designed, synthesized and evaluated for their anti-tuberculosis (anti-TB) and anti-inflammatory activities. The minimum inhibitory concentration (MIC) of the newly synthesized compound was tested against Mycobacterium tuberculosis H37RV. Among the tested compounds,
[...] Read more.
A series of indeno[1,2-c]quinoline derivatives were designed, synthesized and evaluated for their anti-tuberculosis (anti-TB) and anti-inflammatory activities. The minimum inhibitory concentration (MIC) of the newly synthesized compound was tested against Mycobacterium tuberculosis H37RV. Among the tested compounds, (E)-N′-[6-(4-hydroxypiperidin-1-yl)-11H-indeno[1,2-c]quinolin-11-ylidene]isonicotino-hydrazide (12), exhibited significant activities against the growth of M. tuberculosis (MIC values of 0.96 μg/mL) with a potency approximately equal to that of isoniazid (INH), an anti-TB drug. Important structure features were analyzed by quantitative structure–activity relationship (QSAR) analysis to give better insights into the structure determinants for predicting the anti-TB activity. The anti-inflammatory activity was induced by superoxide anion generation and neutrophil elastase (NE) release using the formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLF)-activated human neutrophils method. Results indicated that compound 12 demonstrated a potent dual inhibitory effect on NE release and superoxide anion generation with IC50 values of 1.76 and 1.72 μM, respectively. Our results indicated that compound 12 is a potential lead compound for the discovery of dual anti-TB and anti-inflammatory drug candidates. In addition, 6-[3-(hydroxymethyl)piperidin-1-yl]-9-methoxy-11H-indeno[1,2-c]quinolin-11-one (4g) showed a potent dual inhibitory effect on NE release and superoxide anion generation with IC50 values of 0.46 and 0.68 μM, respectively, and is a potential lead compound for the discovery of anti-inflammatory drug candidates. Full article
(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)
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Open AccessArticle Synthesis and Evaluation of Antimicrobial Activity of [R4W4K]-Levofloxacin and [R4W4K]-Levofloxacin-Q Conjugates
Molecules 2017, 22(6), 957; doi:10.3390/molecules22060957
Received: 15 May 2017 / Revised: 6 June 2017 / Accepted: 6 June 2017 / Published: 8 June 2017
Cited by 1 | PDF Full-text (775 KB) | HTML Full-text | XML Full-text
Abstract
The development of a new class of antibiotics to fight bacterial resistance is a time-consuming effort associated with high-cost and commercial risks. Thus, modification, conjugation or combination of existing antibiotics to enhance their efficacy is a suitable strategy. We have previously reported that
[...] Read more.
The development of a new class of antibiotics to fight bacterial resistance is a time-consuming effort associated with high-cost and commercial risks. Thus, modification, conjugation or combination of existing antibiotics to enhance their efficacy is a suitable strategy. We have previously reported that the amphiphilic cyclic peptide [R4W4] had antibacterial activity with a minimum inhibitory concentration (MIC) of 2.97 µg/mL against Methicillin-resistant Staphylococcus aureus (MRSA). Herein, we hypothesized that conjugation or combination of the amphiphilic cyclic peptide [R4W4] with levofloxacin or levofloxacin-Q could improve the antibacterial activity of levofloxacin and levofloxacin-Q. Fmoc/tBu solid-phase chemistry was employed to synthesize conjugates of [R4W4K]-levofloxacin-Q and [R4W4K]-levofloxacin. The carboxylic acid group of levofloxacin or levofloxacin-Q was conjugated with the amino group of β-alanine attached to lysine in the presence of 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HBTU) and N,N-diisopropylethylamine (DIPEA) for 3 h to afford the products. Antibacterial assays were conducted to determine the potency of conjugates [R4W4K]-levofloxacin-Q and [R4W4K]-levofloxacin against MRSA and Klebsiella pneumoniae. Although levofloxacin-Q was inactive even at a concentration of 128 µg/mL, [R4W4K]-levofloxacin-Q conjugate and the corresponding physical mixture showed MIC values of 8 µg/mL and 32 µg/mL against MRSA and Klebsiella pneumonia, respectively, possibly due to the activity of the peptide. On the other hand, [R4W4K]-levofloxacin conjugate (MIC = 32 µg/mL and MIC = 128 µg/mL) and the physical mixture (MIC = 8 µg/mL and 32 µg/mL) was less active than levofloxacin (MIC = 2 µg/mL and 4 = µg/mL) against MRSA and Klebsiella pneumoniae, respectively. The data showed that the conjugation of levofloxacin with [R4W4K] significantly reduced the antibacterial activity compared to the parent analogs, while [R4W4K]-levofloxacin-Q conjugate was more significantly potent than levofloxacin-Q alone. Full article
(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)
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Open AccessArticle Himatanthus drasticus Leaves: Chemical Characterization and Evaluation of Their Antimicrobial, Antibiofilm, Antiproliferative Activities
Molecules 2017, 22(6), 910; doi:10.3390/molecules22060910
Received: 22 April 2017 / Revised: 25 May 2017 / Accepted: 27 May 2017 / Published: 31 May 2017
Cited by 2 | PDF Full-text (1924 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Plant-derived products have played a fundamental role in the development of new therapeutic agents. This study aimed to analyze antimicrobial, antibiofilm, cytotoxicity and antiproliferative potentials of the extract and fractions from leaves of Himatanthus drasticus, a plant from the Apocynaceae family. After
[...] Read more.
Plant-derived products have played a fundamental role in the development of new therapeutic agents. This study aimed to analyze antimicrobial, antibiofilm, cytotoxicity and antiproliferative potentials of the extract and fractions from leaves of Himatanthus drasticus, a plant from the Apocynaceae family. After harvesting, H. drasticus leaves were macerated and a hydroalcoholic extract (HDHE) and fractions were prepared. Antimicrobial tests, such as agar-diffusion, Minimum Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) were carried out against several bacterial species. Staphylococcus aureus, Pseudomonas aeruginosa, Listeria monocytogenes and Klebsiella pneumoniae were inhibited by at least one extract or fraction in the agar-diffusion assay (inhibition halos from 12 mm to 30 mm). However, the lowest MIC value was found for HDHE against K. pneumoniae. In addition, HDHE and its fractions were able to inhibit biofilm formation at sub-inhibitory concentrations (780 µg/mL and 1.56 µg/mL). As the best activities were found for HDHE, we selected it for further assays. HDHE was able to increase ciprofloxacin (CIP) activity against K. pneumoniae, displaying synergistic (initial concentration CIP + HDHE: 2 µg/mL + 600 µg/mL and 2.5 µg/mL + 500 µg/mL) and additive effects (CIP + HDHE: 3 µg/mL + 400 µg/mL). This action seems to be associated with the alteration in bacterial membrane permeability induced by HDHE (as seen by propidium iodide labeling). This extract was non-toxic for red blood cell or human peripheral blood mononuclear cells (PBMCs). Additionally, it inhibited the lipopolysaccharide-induced proliferation of PBMCs. The following compounds were detected in HDHE using HPLC-ESI-MS analysis: plumieride, plumericin or isoplumericin, rutin, quercetin and derivatives, and chlorogenic acid. Based on these results we suggest that compounds from H. drasticus have antimicrobial and antibiofilm activities against K. pneumoniae and display low cytotoxicity and anti-proliferative action in PBMC stimulated with lipopolysaccharide. Full article
(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)
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Open AccessArticle Evaluation of the Mycobactericidal Effect of Thio-functionalized Carbohydrate Derivatives
Molecules 2017, 22(5), 812; doi:10.3390/molecules22050812
Received: 30 March 2017 / Revised: 5 May 2017 / Accepted: 11 May 2017 / Published: 16 May 2017
Cited by 2 | PDF Full-text (883 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Sugars with heteroatoms other than oxygen have attained considerable importance in glycobiology and in drug design since they are often more stable in blood plasma due to their resistance to enzymes, such as glycosidases, phosphorylases and glycosyltransferases. The replacement of oxygen atoms in
[...] Read more.
Sugars with heteroatoms other than oxygen have attained considerable importance in glycobiology and in drug design since they are often more stable in blood plasma due to their resistance to enzymes, such as glycosidases, phosphorylases and glycosyltransferases. The replacement of oxygen atoms in sugars with sulfur forms thio-sugars, which are potentially useful for the treatment of diabetes and some bacterial and viral infections. Here, we evaluated the antibacterial activity of thio-functionalized carbohydrate derivatives. A set of 21 compounds was screened against acid-fast Mycobacterium tuberculosis (Mtb), gram-negative Escherichia coli and gram-positive Staphylococcus aureus. The tested carbohydrate derivatives were most effective against tubercle bacilli, with as many as five compounds (thioglycoside 6, thiosemicarbazone 16A, thiosemicarbazone 20, aminothiadiazole 23, and thiazoline 26) inhibiting its growth with MIC50 ≤ 50 µM/CFU. Only two compounds (aminothiadiazole 23 and thiazoline 26) were able to inhibit the growth of E. coli at concentrations below 1 mM, and one of them, aminothiadiazole 23, inhibited the growth of S. aureus at a concentration ≤1 mM. The five compounds affecting the growth of mycobacteria were either thiodisaccharides (6, 16A, and 20) or thioglycosides (23 and 26). All of these compounds (6, 16A, 20, 23, and 26) were able to inhibit the growth of Mtb deposited within human macrophages. However, three of the five selected compounds (6, 23, and 26) exhibited relatively high cytotoxicity in mouse fibroblasts at micromolar concentrations. The selected thio-sugars are very promising compounds, thus making them candidates for further modifications that would decrease their cytotoxicity against eukaryotic cells without affecting their antimycobacterial potential. Full article
(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)
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Open AccessArticle Synthesis and Evaluation of Essential Oil-Derived β-Methoxyacrylate Derivatives as High Potential Fungicides
Molecules 2017, 22(5), 763; doi:10.3390/molecules22050763
Received: 31 March 2017 / Revised: 5 May 2017 / Accepted: 5 May 2017 / Published: 8 May 2017
PDF Full-text (4145 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Essential oils (EOs) are plant-derived aroma compounds with a wide range of biological activity, but their actions are slow, and they are typically unstable to light or heat, difficult to extract and so on. To find highly potential fungicides derived from natural EOs,
[...] Read more.
Essential oils (EOs) are plant-derived aroma compounds with a wide range of biological activity, but their actions are slow, and they are typically unstable to light or heat, difficult to extract and so on. To find highly potential fungicides derived from natural EOs, a series of essential oil-based β-methoxyacrylate derivatives have been designed and synthesized. The target compounds have been screened for their potential fungicidal activity against eleven species of plant pathogen fungi, including Alternaria alternata, Phomopsis adianticola, Pestalotiopsis theae, Sclerotinia sclerotiorum, etc. Compared with intermediates I, the parent essential oils and azoxystrobin, almost all of essential oil-based β-methoxyacrylate derivatives exhibited significantly better fungicidal activity. Further investigation revealed that some compounds showed remarkable inhibitory activities against Pestalotiopsis theae, Phomopsis adianticola, Sclerotinia sclerotiorum and Magnapothe grisea at different concentrations in contrast to the commercial product azoxystrobin. Compound II-8 exhibited particularly significant fungicidal activity. Full article
(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)
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Open AccessArticle Design, Synthesis and Fungicidal Activity of 2-Substituted Phenyl-2-oxo-, 2-Hydroxy- and 2-Acyloxyethylsulfonamides
Molecules 2017, 22(5), 738; doi:10.3390/molecules22050738
Received: 10 April 2017 / Revised: 29 April 2017 / Accepted: 30 April 2017 / Published: 4 May 2017
Cited by 1 | PDF Full-text (851 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Sulfonyl-containing compounds, which exhibit a broad spectrum of biological activities, comprise a substantial proportion of and play a vital role, not only in medicines but also in agrochemicals. As a result increasing attention has been paid to the research and development of sulfonyl
[...] Read more.
Sulfonyl-containing compounds, which exhibit a broad spectrum of biological activities, comprise a substantial proportion of and play a vital role, not only in medicines but also in agrochemicals. As a result increasing attention has been paid to the research and development of sulfonyl derivatives. A series of thirty-eight 2-substituted phenyl-2-oxo- III, 2-hydroxy- IV and 2-acyloxyethylsulfonamides V were obtained and their structures confirmed by IR, 1H-NMR, and elemental analysis. The in vitro and in vivo bioactivities against two Botrytis cinerea strains, DL-11 and HLD-15, which differ in their sensitivity to procymidone, were evaluated. The in vitro activity results showed that the EC50 values of compounds V-1 and V-9 were 0.10, 0.01 mg L−1 against the sensitive strain DL-11 and 3.32, 7.72 mg L−1 against the resistant strain HLD-15, respectively. For in vivo activity against B. cinerea, compound V-13 and V-14 showed better control effect than the commercial fungicides procymidone and pyrimethanil. The further in vitro bioassay showed that compounds III, IV and V had broad fungicidal spectra against different phytopathogenic fungi. Most of the title compounds showed high fungicidal activities, which could be used as lead compounds for further developing novel fungicidal compounds against Botrytis cinerea. Full article
(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)
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Open AccessArticle Synthesis and Antiviral Activity of Novel 1,4-Pentadien-3-one Derivatives Containing a 1,3,4-Thiadiazole Moiety
Molecules 2017, 22(4), 658; doi:10.3390/molecules22040658
Received: 30 March 2017 / Revised: 15 April 2017 / Accepted: 18 April 2017 / Published: 21 April 2017
Cited by 2 | PDF Full-text (521 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
1,4-Pentadien-3-one derivatives derived from curcumin possess excellent inhibitory activity against plant viruses. On the basis of this finding, a series of novel 1,4-pentadien-3-one derivatives containing a 1,3,4-thiadiazole moiety were designed and synthesized, and their structures confirmed by IR, 1H-NMR, and 13C-NMR
[...] Read more.
1,4-Pentadien-3-one derivatives derived from curcumin possess excellent inhibitory activity against plant viruses. On the basis of this finding, a series of novel 1,4-pentadien-3-one derivatives containing a 1,3,4-thiadiazole moiety were designed and synthesized, and their structures confirmed by IR, 1H-NMR, and 13C-NMR spectroscopy and elemental analysis. The antiviral activities of the title compounds were evaluated against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) in vivo. The assay results showed that most of compounds had remarkable antiviral activities against TMV and CMV, among which compounds 4b, 4h, 4i, 4k, 4o, and 4q exhibited good curative, protection, and inactivation activity against TMV. Compounds 4h, 4i, 4k, 4l, 4o, and 4q exhibited excellent protection activity against TMV, with EC50 values of 105.01, 254.77, 135.38, 297.40, 248.18, and 129.87 μg/mL, respectively, which were superior to that of ribavirin (457.25 µg/mL). In addition, preliminary SARs indicated that small electron-withdrawing groups on the aromatic ring were favorable for anti-TMV activity. This finding suggests that 1,4-pentadien-3-one derivatives containing a 1,3,4-thiadiazole moiety may be considered as potential lead structures for discovering new antiviral agents. Full article
(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)
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Open AccessCommunication Synthesis and Antibacterial Evaluation of Novel 3-Substituted Ocotillol-Type Derivatives as Leads
Molecules 2017, 22(4), 590; doi:10.3390/molecules22040590
Received: 1 March 2017 / Revised: 31 March 2017 / Accepted: 3 April 2017 / Published: 7 April 2017
Cited by 2 | PDF Full-text (3368 KB) | HTML Full-text | XML Full-text
Abstract
Due to the rapidly growing bacterial antibiotic-resistance and the scarcity of novel agents in development, bacterial infection is still a global problem. Therefore, new types of antibacterial agents, which are effective both alone and in combination with traditional antibiotics, are urgently needed. In
[...] Read more.
Due to the rapidly growing bacterial antibiotic-resistance and the scarcity of novel agents in development, bacterial infection is still a global problem. Therefore, new types of antibacterial agents, which are effective both alone and in combination with traditional antibiotics, are urgently needed. In this paper, a series of antibacterial ocotillol-type C-24 epimers modified from natural 20(S)-protopanaxadiol were synthesized and evaluated for their antibacterial activity. According to the screening results of Gram-positive bacteria (B. subtilis 168 and MRSA USA300) and Gram-negative bacteria (P. aer PAO1 and A. baum ATCC19606) in vitro, the derivatives exhibited good antibacterial activity, particularly against Gram-positive bacteria with an minimum inhibitory concentrations (MIC) value of 2–16 µg/mL. The subsequent synergistic antibacterial assay showed that derivatives 5c and 6c enhanced the susceptibility of B. subtilis 168 and MRSA USA300 to chloramphenicol (CHL) and kanamycin (KAN) (FICI < 0.5). Our data showed that ocotillol-type derivatives with long-chain amino acid substituents at C-3 were good leads against antibiotic-resistant pathogens MRSA USA300, which could improve the ability of KAN and CHL to exhibit antibacterial activity at much lower concentrations with reduced toxicity. Full article
(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)
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Open AccessArticle The Novel Property of Heptapeptide of Microcin C7 in Affecting the Cell Growth of Escherichia coli
Molecules 2017, 22(3), 432; doi:10.3390/molecules22030432
Received: 15 December 2016 / Accepted: 6 March 2017 / Published: 8 March 2017
Cited by 1 | PDF Full-text (12366 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
Microcin C7 (McC), widely distributed in enterobacteria, is a promising antibiotic against antibiotic resistance [...] Full article
(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)
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Open AccessFeature PaperArticle Anti-Bacterial and Anti-Fungal Activity of Xanthones Obtained via Semi-Synthetic Modification of α-Mangostin from Garcinia mangostana
Molecules 2017, 22(2), 275; doi:10.3390/molecules22020275
Received: 14 December 2016 / Revised: 7 February 2017 / Accepted: 8 February 2017 / Published: 12 February 2017
Cited by 1 | PDF Full-text (3248 KB) | HTML Full-text | XML Full-text | Supplementary Files
Abstract
The microbial contamination in food packaging has been a major concern that has paved the way to search for novel, natural anti-microbial agents, such as modified α-mangostin. In the present study, twelve synthetic analogs were obtained through semi-synthetic modification of α-mangostin by Ritter
[...] Read more.
The microbial contamination in food packaging has been a major concern that has paved the way to search for novel, natural anti-microbial agents, such as modified α-mangostin. In the present study, twelve synthetic analogs were obtained through semi-synthetic modification of α-mangostin by Ritter reaction, reduction by palladium-carbon (Pd-C), alkylation, and acetylation. The evaluation of the anti-microbial potential of the synthetic analogs showed higher bactericidal activity than the parent molecule. The anti-microbial studies proved that I E showed high anti-bacterial activity whereas I I showed the highest anti-fungal activity. Due to their microbicidal potential, modified α-mangostin derivatives could be utilized as active anti-microbial agents in materials for the biomedical and food industry. Full article
(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)
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Open AccessArticle Antifungal Activity of Oleuropein against Candida albicans—The In Vitro Study
Molecules 2016, 21(12), 1631; doi:10.3390/molecules21121631
Received: 1 November 2016 / Revised: 21 November 2016 / Accepted: 24 November 2016 / Published: 28 November 2016
Cited by 1 | PDF Full-text (965 KB) | HTML Full-text | XML Full-text
Abstract
In the present study we investigated activity of oleuropein, a complex phenol present in large quantities in olive tree products, against opportunistic fungal pathogen Candida albicans. Oleuropein was found to have in vitro antifungal activity with a minimal inhibitory concentration (MIC) value
[...] Read more.
In the present study we investigated activity of oleuropein, a complex phenol present in large quantities in olive tree products, against opportunistic fungal pathogen Candida albicans. Oleuropein was found to have in vitro antifungal activity with a minimal inhibitory concentration (MIC) value of 12.5 mg·mL−1. Morphological changes in the nuclei after staining with fluorescent DNA-binding dyes revealed that apoptosis was a primary mode of cell death in the analyzed samples treated with subinhibitory concentrations of oleuropein. Our results suggest that this antifungal agent targets virulence factors essential for establishment of the fungal infection. We noticed that oleuropein modulates morphogenetic conversion and inhibits filamentation of C. albicans. The hydrophobicity assay showed that oleuropein in sub-MIC values has significantly decreased, in both aerobic and anaerobic conditions, the cellular surface hydrophobicity (CSH) of C. albicans, a factor associated with adhesion to epithelial cells. It was also demonstrated that the tested compound inhibits the activity of SAPs, cellular enzymes secreted by C. albicans, which are reported to be related to the pathogenicity of the fungi. Additionally, we detected that oleuropein causes a reduction in total sterol content in the membrane of C. albicans cells, which might be involved in the mechanism of its antifungal activity. Full article
(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)
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Open AccessArticle Structural Analysis of Sortase A Inhibitors
Molecules 2016, 21(11), 1591; doi:10.3390/molecules21111591
Received: 25 October 2016 / Revised: 12 November 2016 / Accepted: 19 November 2016 / Published: 22 November 2016
Cited by 3 | PDF Full-text (1148 KB) | HTML Full-text | XML Full-text
Abstract
Bacterial sortases are cysteine transpeptidases that regulate the covalent linkage of several surface protein virulence factors in Gram-positive bacteria. Virulence factors play significant roles in adhesion, invasion of host tissues, biofilm formation and immune evasion, mediating the bacterial pathogenesis and infectivity. Therefore, sortases
[...] Read more.
Bacterial sortases are cysteine transpeptidases that regulate the covalent linkage of several surface protein virulence factors in Gram-positive bacteria. Virulence factors play significant roles in adhesion, invasion of host tissues, biofilm formation and immune evasion, mediating the bacterial pathogenesis and infectivity. Therefore, sortases are emerging as important targets for the design of new anti-infective agents. We employed a computational study, based on structure derived descriptors and molecular fingerprints, in order to develop simple classification methods which could allow predicting low active or high active SrtA inhibitors. Our results indicate that a highly active SrtA inhibitor has a molecular weight ranging between 180 and 600, contains one up to four nitrogen atoms, up to three oxygen atoms and under 18 hydrogen atoms. Also the hydrogen acceptor number and the molecular flexibility, as assessed by the number of rotatable bounds, have emerged as the most relevant descriptors for SrtA affinity. The Bemis-Murcko scaffolding revealed favoured scaffolds as containing at least two ring structures bonded directly or merged in a condensed cycle. This data represent a valuable tool for identifying new potent SrtA inhibitors, potential anti-virulence agents targeted against Gram-positive bacteria, including multiresistant strains. Full article
(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)
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Open AccessArticle Synthesis and Biological Evaluation of Benzimidazole Phenylhydrazone Derivatives as Antifungal Agents against Phytopathogenic Fungi
Molecules 2016, 21(11), 1574; doi:10.3390/molecules21111574
Received: 13 October 2016 / Revised: 8 November 2016 / Accepted: 12 November 2016 / Published: 22 November 2016
Cited by 1 | PDF Full-text (1651 KB) | HTML Full-text | XML Full-text
Abstract
A series of benzimidazole phenylhydrazone derivatives (6a6ai) were synthesized and characterized by 1H-NMR, ESI-MS, and elemental analysis. The structure of 6b was further confirmed by single crystal X-ray diffraction as (E)-configuration. All the compounds were screened
[...] Read more.
A series of benzimidazole phenylhydrazone derivatives (6a6ai) were synthesized and characterized by 1H-NMR, ESI-MS, and elemental analysis. The structure of 6b was further confirmed by single crystal X-ray diffraction as (E)-configuration. All the compounds were screened for antifungal activity against Rhizoctonia solani and Magnaporthe oryzae employing a mycelium growth rate method. Compound 6f exhibited significant inhibitory activity against R. solani and M. oryzae with the EC50 values of 1.20 and 1.85 μg/mL, respectively. In vivo testing demonstrated that 6f could effectively control the development of rice sheath blight (RSB) and rice blast (RB) caused by the above two phytopathogens. This work indicated that the compound 6f with a benzimidazole phenylhydrazone scaffold could be considered as a leading structure for the development of novel fungicides. Full article
(This article belongs to the Special Issue Frontiers in Antimicrobial Drug Discovery and Design)
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