scholarly journals Synthesis of Novel Benzylic 1,2,3-triazole-4-carboxamides and their in vitro Activity Against Clinically Common Fungal Species

2021 ◽  
Vol 65 (2) ◽  
Author(s):  
Davir González-Calderón ◽  
Ricardo García-Monroy ◽  
Alejandra Ramírez-Villalva ◽  
Salvador Mastachi-Loza ◽  
José G. Aguirre-de Paz ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Rhizopus Oryzae ◽  
Fungal Species ◽  
In Vitro Assays ◽  
Trichosporon Cutaneum ◽  
Mucor Hiemalis ◽  
One Pot ◽  
Reference Drug ◽  
Para Determinar

Abstract. A library of novel benzylic 1,2,3-triazole-4-carboxamides (3a-m) were obtained with acceptable yields via a one-pot procedure. The series of compounds was screened for fungicidal activity and evaluated in vitro against four filamentous fungi and four Candida species. The former consisted of Aspergillus fumigatus, Trichosporon cutaneum, Rhizopus oryzae and Mucor hiemalis, and the latter C. krusei, C. albicans, C. utilis and C. glabrata. According to the in vitro assays, 3d and 3e were the most efficient fungicidal agents (of all the test compounds) against R. oryzae, even better than the reference drug (itraconazole). Thus, 3d and 3e represent important scaffolds that can be modified to increase antifungal activity. Additionally, they are candidates for complementary studies on the inhibition of clinical infections produced by Rhizopus spp. strains.   Resumen. Se obtuvo una librería de nuevos bencil 1,2,3-triazoles-4-carboxamidas (3a-m) con rendimientos aceptables mediante un procedimiento one-pot. La serie de compuestos se seleccionó para determinar la actividad fungicida llevando a cabo una evaluación in vitro contra cuatro hongos filamentosos y cuatro especies de Candida. Los primeros consistieron en Aspergillus fumigatus, Trichosporon cutaneum, Rhizopus oryzae y Mucor hiemalis, mientras que para las segundas especies, esta fueron C. krusei, C. albicans, C. utilis y C. glabrata. Según los ensayos in vitro, 3d y 3e fueron los agentes fungicidas más eficaces (de todos los compuestos de prueba) contra R. oryzae, incluso mejores que el fármaco de referencia (itraconazol). Por tanto, 3d y 3e representan importantes núcleos que podrían modificarse para aumentar la actividad antifúngica, siendo excelentes candidatos para estudios complementarios sobre la inhibición de infecciones clínicas producidas por Rhizopus spp.

scholarly journals Structural and Functional Analysis of Horse Cathelicidin Peptides

2001 ◽  
Vol 45 (3) ◽  
pp. 715-722 ◽  
Author(s):  
Barbara Skerlavaj ◽  
Marco Scocchi ◽  
Renato Gennaro ◽  
Angela Risso ◽  
Margherita Zanetti
Keyword(s):  
Strong Dependence ◽  
Functional Characterization ◽  
Fungal Species ◽  
Helical Conformation ◽  
In Vitro Assays ◽  
Synthetic Analogue ◽  
Salt Medium ◽  
Cdna Sequences ◽  
Low Ionic Strength

ABSTRACT Cathelicidin-derived antimicrobial peptides are a component of the peptide-based host defense of neutrophils and epithelia, with a widespread distribution in mammals. We recently reported the cDNA sequences of three putative horse myeloid cathelicidins, named eCATH-1, -2, and -3. A Western analysis was performed to investigate their presence in neutrophils and processing to mature peptides. eCATH-2 and eCATH-3, but not eCATH-1, were found to be present in uncleaved forms in horse neutrophils. The corresponding mature peptides were detected in inflammatory sites, suggesting that processing of the propeptides takes place upon neutrophil activation. A functional characterization was then performed with synthetic eCATH peptides. Circular dichroism measurements indicated an amphipathic α-helical conformation of these peptides in an anisotropic environment, and in vitro assays revealed a potent activity and a broad spectrum of antimicrobial activity for eCATH-1 and a somewhat more restricted spectrum of activity for eCATH-2. Conversely, a strong dependence on salt concentration was observed when the activity of eCATH-3 was tested. This peptide efficiently killed bacteria and some fungal species, i.e.,Cryptococcus neoformans and Rhodotorula rubra, in low-ionic-strength media, but the activity was inhibited in the presence of physiological salt medium. This behavior could be modified by modulating the amphipathicity of the molecule. In fact, the synthetic analogue LLK-eCATH-3, with a slightly modified sequence that increases the hydrophobic moment of the peptide, displayed a potent activity in physiological salt medium against the strains resistant to eCATH-3 under these conditions.

scholarly journals Synergy, Pharmacodynamics, and Time-Sequenced Ultrastructural Changes of the Interaction between Nikkomycin Z and the Echinocandin FK463 against Aspergillus fumigatus

2001 ◽  
Vol 45 (12) ◽  
pp. 3310-3321 ◽  
Author(s):  
Christine C. Chiou ◽  
Nikolaos Mavrogiorgos ◽  
Elizabeth Tillem ◽  
Richard Hector ◽  
Thomas J. Walsh
Keyword(s):  
Cell Wall ◽  
Aspergillus Fumigatus ◽  
Rhizopus Oryzae ◽  
Ultrastructural Changes ◽  
Synergistic Activity ◽  
Partial Recovery ◽  
Electron Microscopic ◽  
Wide Range ◽  
Nikkomycin Z

ABSTRACT We investigated the potential synergy between two cell wall-active agents, the echinocandin FK463 (FK) and the chitin synthase inhibitor nikkomycin Z (NZ), against 16 isolates of filamentous fungi. Susceptibility testing was performed with a broth macrodilution procedure by NCCLS methods. The median minimal effective concentration (MEC) of FK against all Aspergillus species was 0.25 μg/ml (range, 0.05 to 0.5 μg/ml). For Fusarium solaniand Rhizopus oryzae, MECs of FK were >512 μg/ml. The median MEC of NZ against Aspergillus fumigatus was 32 μg/ml (range, 8 to 64 μg/ml), and that against R. oryzae was 0.5 μg/ml (range, 0.06 to 2 μg/ml); however, for the other Aspergillus species, as well as F. solani, MECs were >512 μg/ml. A checkerboard inhibitory assay demonstrated synergy against A. fumigatus (median fractional inhibitory concentration index = 0.312 [range, 0.15 to 0.475]). The effect was additive to indifferent against R. oryzae and indifferent against other Aspergillus spp. and F. solani. We further investigated the pharmacodynamics of hyphal damage by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and examined the time-sequenced changes in hyphal ultrastructure. Significant synergistic hyphal damage was demonstrated with the combination of NZ (2 to 32 μg/ml) and FK (0.03 to 0.5 μg/ml) over a wide range of concentrations (P < 0.001). The synergistic effect was most pronounced after 12 h of incubation and was sustained through 24 h. Time-sequenced light and electron microscopic studies demonstrated that structural alterations of hyphae were profound, with marked transformation of hyphae to blastospore-like structures, in the presence of FK plus NZ, while fungi treated with a single drug showed partial recovery at 24 h. The methods used in this study may be applicable to elucidating the activity and interaction of other cell wall-active agents. In summary, these two cell wall-targeted antifungal agents, FK and NZ, showed marked time-dependent in vitro synergistic activity against A. fumigatus.

scholarly journals Design, synthesis, and discovery of novel oxindoles bearing 3-heterocycles as species-specific and combinatorial agents in eradicating Staphylococcus species

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Jonghoon Shin ◽  
Krishna Bahadur Somai Magar ◽  
Jungwoon Lee ◽  
Kwang-sun Kim ◽  
Yong Rok Lee
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Multidrug Resistant ◽  
Cellular Level ◽  
One Pot ◽  
Design Synthesis ◽  
Reference Drug ◽  
As Species ◽  
Species Specific

Abstract A series of new functionalized 3-indolylindolin-2-ones, 3-(1-methylpyrrol-2-yl)indolin-2-ones, and 3-(thiophen-2-yl)indolin-2-ones were synthesized by using novel indium (III)-catalysed reaction of various 3-diazoindolin-2-ones with indoles, 1-methylpyrrole, or thiophene via one-pot procedure. The newly synthesized compounds were characterized and screened for their in vitro antibacterial activity against various Staphylococcus species, including methicillin-resistant Staphylococcus aureus. results revealed that five compounds KS15, KS16, KS17, KS19, and KS20 exhibited potent and specific antibacterial activity against Staphylococcus species albeit inactive against Gram-negative bacteria. Especially, compounds exhibited superior antibacterial potency against Staphylococcus epidermidis compared to the reference drug streptomycin. The most potential compound KS16 also increased the susceptibility of Staphylococcus aureus to ciprofloxacin, gentamicin, kanamycin, and streptomycin. Among them, KS16 was found to be a synergistic compound with gentamicin and kanamycin. Furthermore, the cellular level of autolysin protein was increased from the KS16-treated Staphylococcus aureus cells. Finally, in vitro CCK-8 assays showed that KS16 exhibited no cytotoxicity at the minimum inhibitory concentrations used for killing Staphylococcus species. From all our results, novel oxindole compounds directly have lethal action or boost existing antibiotic power with the reduction of doses and toxicity in the treatment of multidrug-resistant Staphylococcus species.

Molecular Docking and Quantum Studies of Lawsone Dimers Derivatives: New Investigation of Antioxidant Behavior and Antifungal Activity

2020 ◽  
Vol 20 (3) ◽  
pp. 182-191 ◽  
Author(s):  
Aldo S. de Oliveira ◽  
David L. Palomino-Salcedo ◽  
Eduardo Zapp ◽  
Daniela Brondani ◽  
Thaynara D. Hoppe ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Reducing Power ◽  
Public Health Problem ◽  
Resistance Mechanisms ◽  
Docking Studies ◽  
Fungal Species ◽  
Antioxidant Potential ◽  
In Vitro Assays ◽  
Major Public Health Problem

Background: In general, fungal species are characterized by their opportunistic character and can trigger various infections in immunocompromised hosts. The emergence of infections associated with high mortality rates is due to the resistance mechanisms that these species develop. Methods: This phenomenon of resistance denotes the need for the development of new and effective therapeutic approaches. In this paper, we report the investigation of the antioxidant and antifungal behavior of dimeric naphthoquinones derived from lawsone whose antimicrobial and antioxidant potential has been reported in the literature. Results: Seven fungal strains were tested, and the antioxidant potential was tested using the combination of the methodologies: reducing power, total antioxidant capacity and cyclic voltammetry. Molecular docking studies (PDB ID 5V5Z and 1EA1) were conducted which allowed the derivation of structureactivity relationships (SAR). Compound 1-i, derived from 3-methylfuran-2-carbaldehyde showed the highest antifungal potential with an emphasis on the inhibition of Candida albicans species (MIC = 0.5 µg/mL) and the highest antioxidant potential. Conclusion: A combination of molecular modeling data and in vitro assays can help to find new solutions to this major public health problem.

scholarly journals Gliotoxin Is a Virulence Factor of Aspergillus fumigatus: gliP Deletion Attenuates Virulence in Mice Immunosuppressed with Hydrocortisone

2007 ◽  
Vol 6 (9) ◽  
pp. 1562-1569 ◽  
Author(s):  
Janyce A. Sugui ◽  
Julian Pardo ◽  
Yun C. Chang ◽  
Kol A. Zarember ◽  
Glenn Nardone ◽  
...  
Keyword(s):  
Aspergillus Fumigatus ◽  
Virulence Factor ◽  
High Performance ◽  
Superoxide Production ◽  
In Vitro Assays ◽  
Mouse Strains ◽  
Human Neutrophils ◽  
Pathogenic Potential ◽  
Chromatography Analysis

ABSTRACT Gliotoxin is an immunosuppressive mycotoxin long suspected to be a potential virulence factor of Aspergillus fumigatus. Recent studies using mutants lacking gliotoxin production, however, suggested that the mycotoxin is not important for pathogenesis of A. fumigatus in neutropenic mice resulting from treatment with cyclophosphomide and hydrocortisone. In this study, we report on the pathobiological role of gliotoxin in two different mouse strains, 129/Sv and BALB/c, that were immunosuppressed by hydrocortisone alone to avoid neutropenia. These strains of mice were infected using the isogenic set of a wild type strain (B-5233) and its mutant strain (gliPΔ) and the the glip reconstituted strain (gliP R). The gliP gene encodes a nonribosomal peptide synthase that catalyzes the first step in gliotoxin biosynthesis. The gliPΔ strain was significantly less virulent than strain B-5233 or gliP R in both mouse models. In vitro assays with culture filtrates (CFs) of B-5233, gliPΔ, and gliP R strains showed the following: (i) deletion of gliP abrogated gliotoxin production, as determined by high-performance liquid chromatography analysis; (ii) unlike the CFs from strains B-5233 and gliP R, gliPΔ CFs failed to induce proapoptotic processes in EL4 thymoma cells, as tested by Bak conformational change, mitochondrial-membrane potential disruption, superoxide production, caspase 3 activation, and phosphatidylserine translocation. Furthermore, superoxide production in human neutrophils was strongly inhibited by CFs from strain B-5233 and the gliP R strain, but not the gliPΔ strain. Our study confirms that gliotoxin is an important virulence determinant of A. fumigatus and that the type of immunosuppression regimen used is important to reveal the pathogenic potential of gliotoxin.

scholarly journals Antifungal Resistance: Specific Focus on Multidrug Resistance in Candida auris and Secondary Azole Resistance in Aspergillus fumigatus

2018 ◽  
Vol 4 (4) ◽  
pp. 129 ◽  
Author(s):  
Sevtap Arikan-Akdagli ◽  
Mahmoud Ghannoum ◽  
Jacques Meis
Keyword(s):  
Aspergillus Fumigatus ◽  
Molecular Mechanisms ◽  
Multidrug Resistant ◽  
Fungal Species ◽  
Antifungal Resistance ◽  
Current Status ◽  
Clinical Implications ◽  
Azole Resistance ◽  
Candida Auris

Antifungal resistance is a topic of concern, particularly for specific fungal species and drugs. Among these are the multidrug-resistant Candida auris and azole-resistant Aspergillus fumigatus. While the knowledge on molecular mechanisms of resistance is now accumulating, further data are also available for the clinical implications and the extent of correlation of in vitro resistance to clinical outcomes. This review article summarizes the epidemiology of C. auris infections, animal models focusing on the activity of novel antifungal compounds in C. auris infections, virulence factors, and the mechanisms of antifungal resistance for this multi-resistant Candida species. Regarding A. fumigatus, the significance of azoles in the treatment of A. fumigatus infections, reference methods available for the detection of resistance in vitro, molecular mechanisms of secondary azole resistance, routes of acquisition, and clinical implications of in vitro resistance are covered to provide guidance for the current status of azole resistance in A. fumigatus.

Navel Orange Peel Essential Oil To Control Food Spoilage Molds in Potato Slices

2018 ◽  
Vol 81 (9) ◽  
pp. 1496-1502
Author(s):  
YONGQING SHI ◽  
SA HUANG ◽  
YIYAN HE ◽  
JINJING WU ◽  
YUPEI YANG
Keyword(s):  
Essential Oil ◽  
Rhizopus Oryzae ◽  
Microbiological Quality ◽  
Orange Peel ◽  
Fungal Species ◽  
Gas Chromatography Mass Spectrometry ◽  
Navel Orange ◽  
Potato Slices

ABSTRACT The aim of this study was to investigate the efficacy of navel orange, Citrus sinensis (L.) Osbeck, peel essential oil (NOPEO) for inhibiting spoilage fungi in potato slices. Sixteen different components accounting for 99.79% of the headspace components of NOPEO were identified by gas chromatography–mass spectrometry. d-Limonene was the major component of NOPEO. Antifungal activity of NOPEO was tested in vitro and in vivo against four foodborne fungi. A MIC of NOPEO against the four fungal species was 9.40 μL/mLair. NOPEO provided about 74, 74, 73, and 69% protection against Aspergillus niger, Mucor wutungkiao, Penicillium funiculosum, and Rhizopus oryzae at 2.00 μL/mLair concentration, respectively. NOPEO has been demonstrated to significantly improve the microbiological quality of potato slices.

scholarly journals Novel Hit Compounds as Putative Antifungals: The Case of Aspergillus fumigatus

Molecules ◽  
2019 ◽  
Vol 24 (21) ◽  
pp. 3853 ◽  
Author(s):  
Eftichia Kritsi ◽  
Minos-Timotheos Matsoukas ◽  
Constantinos Potamitis ◽  
Anastasia Detsi ◽  
Marija Ivanov ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Aspergillus Fumigatus ◽  
Fungal Pathogens ◽  
Fungal Infections ◽  
Pharmacophore Model ◽  
Antifungal Drugs ◽  
In Vitro Assays ◽  
Minimum Fungicidal Concentration ◽  
Dynamics Simulations

The prevalence of invasive fungal infections has been dramatically increased as the size of the immunocompromised population worldwide has grown. Aspergillus fumigatus is characterized as one of the most widespread and ubiquitous fungal pathogens. Among antifungal drugs, azoles have been the most widely used category for the treatment of fungal infections. However, increasingly, azole-resistant strains constitute a major problem to be faced. Towards this direction, our study focused on the identification of compounds bearing novel structural motifs which may evolve as a new class of antifungals. To fulfil this scope, a combination of in silico techniques and in vitro assays were implemented. Specifically, a ligand-based pharmacophore model was created and served as a 3D search query to screen the ZINC chemical database. Additionally, molecular docking and molecular dynamics simulations were used to improve the reliability and accuracy of virtual screening results. In total, eight compounds, bearing completely different chemical scaffolds from the commercially available azoles, were proposed and their antifungal activity was evaluated using in vitro assays. Results indicated that all tested compounds exhibit antifungal activity, especially compounds 1, 2, and 4, which presented the most promising minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) values and, therefore, could be subjected to further hit to lead optimization.

Sign in / Sign up

Export Citation Format

Share Document