scholarly journals Profiling of Antifungal Activities and In Silico Studies of Natural Polyphenols from Some Plants

Molecules ◽  
2021 ◽  
Vol 26 (23) ◽  
pp. 7164
Author(s):  
Beenish Khanzada ◽  
Nosheen Akhtar ◽  
Mohammad K. Okla ◽  
Saud A. Alamri ◽  
Abdulrahman Al-Hashimi ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Mechanism Of Action ◽  
In Silico ◽  
Fungal Infections ◽  
Mentha Piperita ◽  
Cinnamomum Zeylanicum ◽  
Cinnamomum Tamala ◽  
In Silico Studies ◽  
Antifungal Potential ◽  
Amomum Subulatum

A worldwide increase in the incidence of fungal infections, emergence of new fungal strains, and antifungal resistance to commercially available antibiotics indicate the need to investigate new treatment options for fungal diseases. Therefore, the interest in exploring the antifungal activity of medicinal plants has now been increased to discover phyto-therapeutics in replacement to conventional antifungal drugs. The study was conducted to explore and identify the mechanism of action of antifungal agents of edible plants, including Cinnamomum zeylanicum, Cinnamomum tamala, Amomum subulatum, Trigonella foenumgraecum, Mentha piperita, Coriandrum sativum, Lactuca sativa, and Brassica oleraceae var. italica. The antifungal potential was assessed via the disc diffusion method and, subsequently, the extracts were assessed for phytochemicals and total antioxidant activity. Potent polyphenols were detected using high-performance liquid chromatography (HPLC) and antifungal mechanism of action was evaluated in silico. Cinnamomum zeylanicum exhibited antifungal activity against all the tested strains while all plant extracts showed antifungal activity against Fusarium solani. Rutin, kaempferol, and quercetin were identified as common polyphenols. In silico studies showed that rutin displayed the greatest affinity with binding pocket of fungal 14-alpha demethylase and nucleoside diphosphokinase with the binding affinity (Kd, −9.4 and −8.9, respectively), as compared to terbinafine. Results indicated that Cinnamomum zeylanicum and Cinnamomum tamala exert their antifungal effect possibly due to kaempferol and rutin, respectively, or possibly by inhibition of nucleoside diphosphokinase (NDK) and 14-alpha demethylase (CYP51), while Amomum subulatum and Trigonella foenum graecum might exhibit antifungal potential due to quercetin. Overall, the study demonstrates that plant-derived products have a high potential to control fungal infections.

Synthesis and Biological Activity of 3-(substitutedphenyl)-6-(4-methoxyphenyl)-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine: Part II

2020 ◽  
Vol 18 ◽  
Author(s):  
Niranjan Kaushik ◽  
Nitin Kumar ◽  
Anoop Kumar ◽  
Vikas Sharma
Keyword(s):  
Antifungal Activity ◽  
Opportunistic Infections ◽  
Fungal Infections ◽  
Mass Spectral Data ◽  
Triazole Derivatives ◽  
Mass Spectral ◽  
Fungal Strains ◽  
Antifungal Properties ◽  
Antifungal Potential ◽  
Spectral Data Analysis

Background: Fungal infections are opportunistic infections that become a serious problem to human health. Objective: Considering the antifungal potential of triazole nucleus, the study was carried out with the objective to synthesize some novel triazole derivatives with antifungal potential. Method: 1,2,4-triazole derivatives were synthesized via a two step reaction (reported earlier). The first step involves reaction of substituted benzoic acid with thiocarbohydrazide to form 4-amino-3-(substituted phenyl)-5-mercapto-1, 2, 4-triazole derivatives (1a-1k) while in second step, synthesized compounds (1a-1k) were then subsequently treated with substituted acetophenone to yield substituted (4-methoxyphenyl-7H-[1, 2, 4] triazolo [3, 4-b][1,3,4] thiadiazine derivatives (2a-2k). All synthesized compounds were characterized by IR, 1H NMR, and Mass spectral data analysis and were screened for their antifungal properties against different fungal strains i.e. Candida tropicalis (ATCC-13803, ATCC-20913), Candida albicans (ATCC-60193), Candida inconspicua (ATCC-16783) and Candida glabrata (ATCC-90030, ATCC-2001). Results: Compound 2d displayed better percentage inhibition (26.29%, 24.81%) than fluconazole (24.44%, 22.96%) against ATCC-16783, ATCC-2001 fungal strains respectively at 100µg/ml. Compound 2f also displayed better percentage inhibition (28.51%) against ATCC-90030 as compared to fluconazone (27.4%) at 200 µg/ml. Similarly, compounds 2e and 2j also exhibited better antifungal properties than fluconazole at 200µg/ml. Compound 2e was found most potent against ATCC13803 (30.37%) and ATCC-90030 (30.37%) fungal strains as compared to fluconazole (28.14%, 27.4%) at 200 µg/ml respectively whereas compound 2j exhibited better antifungal activity (28.51%) against ATCC-60193 than fluconazole (27.7%) at 200 µg/ml. Conclusion: The results were in accordance with our assertions for triazole derivatives, as all compounds displayed moderate to good antifungal activity.

scholarly journals Synthesis, Structure-Activity Relationships (SAR) and in Silico Studies of Coumarin Derivatives with Antifungal Activity

2013 ◽  
Vol 14 (1) ◽  
pp. 1293-1309 ◽  
Author(s):  
Rodrigo de Araújo ◽  
Felipe Guerra ◽  
Edeltrudes de O. Lima ◽  
Carlos de Simone ◽  
Josean Tavares ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
In Silico ◽  
Coumarin Derivatives ◽  
Structure Activity Relationships ◽  
Structure Activity ◽  
In Silico Studies

New Benzodioxole-based Pyrazoline Derivatives: Synthesis and Anticandidal, In silico ADME, Molecular Docking Studies

2018 ◽  
Vol 16 (1) ◽  
pp. 82-92 ◽  
Author(s):  
Ahmet Özdemir ◽  
Belgin Sever ◽  
Mehlika Dilek Altıntop
Keyword(s):  
In Silico ◽  
Fungal Infections ◽  
Computational Study ◽  
Docking Studies ◽  
In Vivo Studies ◽  
Heme Group ◽  
In Silico Studies ◽  
Nih 3T3

Background: Azoles are commonly used in the treatment and prevention of fungal infections. They suppress fungal growth by acting on the heme group of lanosterol 14α-demethylase enzyme (CYP51), thus blocking the biosynthesis of ergosterol. </P><P> Objectives: Due to the importance of pyrazolines in the field of antifungal drug design, we aimed to design and synthesize new pyrazoline-based anticandidal agents. Methods: New pyrazoline derivatives were synthesized via the reaction of 1-(chloroacetyl)-3-(2- thienyl)-5-(1,3-benzodioxol-5-yl)-2-pyrazoline with aryl thiols. These compounds were evaluated for their in vitro antifungal effects on Candida species. Docking studies were performed to predict the affinity of the most effective anticandidal agents to substrate binding site of CYP51. Furthermore, MTT assay was performed to determine the cytotoxic effects of the compounds on NIH/3T3 mouse embryonic fibroblast cell line. A computational study for the prediction of ADME properties of all compounds was also carried out. Results: Compounds 5, 8, 10 and 12 were found as the most potent anticandidal agents against Candida albicans and Candida glabrata in this series with the same MIC values of ketoconazole and they also exhibited low toxicity against NIH/3T3 cells. Docking results indicated that all these compounds showed good binding affinity into the active site of CYP51. In particular, chloro substituted compounds 8 and 12 bind to CYP51 through direct coordination with the heme group. According to in silico studies, compound 8 only violated one parameter of Lipinski’s rule of five, making it a potential orally bioavailable agent. Conclusion: Compound 8 was defined as a promising candidate for further in vitro and in vivo studies.

The Inhibitory Effect of Three Essential Oils on Candida rugosa Lipase: In Vitro and In Silico Studies

2020 ◽  
Vol 10 (3) ◽  
pp. 208-215 ◽  
Author(s):  
Talia Serseg ◽  
Khedidja Benarous ◽  
Mohamed Yousfi
Keyword(s):  
Molecular Docking ◽  
Essential Oils ◽  
In Silico ◽  
Candida Rugosa ◽  
Inhibitory Effect ◽  
Mentha Piperita ◽  
Inhibition Mechanism ◽  
Syzygium Aromaticum ◽  
In Silico Studies

Background: Essential oils have been used for centuries. EOs are gaining increasing interest because of their acceptance by consumers and their safe status. For the first time, the effect of essential oils on the inhibition of lipases has been investigated in this work. Objective: We aimed in this study to investigate in vitro the inhibitory effects of the three essential oils of most used spices: Peppermint (Mentha piperita L.), cinnamon (Cinnamomum zeylanicum L.) and Cloves (Syzygium aromaticum L. Merr. et Perry) against Candida rugose lipase. In silico studies using molecular docking have been achieved to study the inhibition mechanism of major compounds of EO: menthol, carvacrol, eugenol and cinnamylaldehyde toward CRL. Methods: The inhibitory effect of three essential oils were determined by candida rugosa enzyme and pNP-L as substrate using spectrophotometry. Autodock vina was used for molecular docking with 50 runs. Results: We have found that these essential oils have a strong inhibitory effect with IC50 values 1.09, 1.78 and 1.13 mg/ml compared with Orlistat 0.06 mg/ml. The results show competitive inhibition for the three major compounds Menthol, Carvacrol and Eugenol with uncompetitive inhibition for Cinnamaldehyde. Different repetition ratios of hydrogen bonds and hydrophobic interactions were observed. The saved interactions were with His449, Ser209, Gly123, Gly124 and Phe344 for all molecules. Conclusion: These observations support using and considering essential oils and their major compounds as good sources for design new drugs to treat candidiasis and other diseases related to Lipases.

scholarly journals Evaluation of Antifungal Activity and Mechanism of Action of Citral againstCandida albicans

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Maria Clerya Alvino Leite ◽  
André Parente de Brito Bezerra ◽  
Janiere Pereira de Sousa ◽  
Felipe Queiroga Sarmento Guerra ◽  
Edeltrudes de Oliveira Lima
Keyword(s):  
Cell Wall ◽  
Antifungal Activity ◽  
Mechanism Of Action ◽  
Cell Walls ◽  
Inhibitory Concentration ◽  
Minimum Fungicidal Concentration ◽  
Antifungal Potential ◽  
Kill Curve ◽  
Time Kill

Candida albicansis a yeast that commensally inhabits the human body and can cause opportunistic or pathogenic infections.Objective. To investigate the antifungal activity of citral againstC. albicans.Methodology. The minimum inhibitory concentration (MIC) and the minimum fungicidal concentration (MFC) were determined by the broth microdilution techniques. We also investigated possible citral action on cell walls (0.8 M sorbitol), cell membranes (citral to ergosterol binding), the time-kill curve, and biological activity on the yeast’s morphology.Results. The MIC and MFC of citral were, respectively, 64 µg/mL and 256 µg/mL. Involvement with the cell wall and ergosterol binding were excluded as possible mechanisms of action. In the morphological interference assay, it was observed that the product inhibited pseudohyphae and chlamydoconidia formation. The MIC and the MFC of citral required only 4 hours of exposure to effectively kill 99.9% of the inoculum.Conclusion. Citral showedin vitroantifungal potential against strains ofC. albicans. Citral’s mechanism of action does not involve the cell wall or ergosterol, and further study is needed to completely describe its effects before being used in the future as a component of new antifungals.

scholarly journals Involvement of GABAA Receptors in the Anxiolytic-Like Effect of Hydroxycitronellal

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Jéssica C. Andrade ◽  
Álefe B. Monteiro ◽  
Humberto H. N. Andrade ◽  
Thallita K. S. N. Gonzaga ◽  
Pablo R. Silva ◽  
...  
Keyword(s):  
Open Field ◽  
Mechanism Of Action ◽  
Gabaa Receptors ◽  
In Silico ◽  
Elevated Plus Maze ◽  
Field Tests ◽  
Plus Maze ◽  
In Silico Studies ◽  
Sedative Effects

Hydroxycitronellal (HC) is a monoterpene present in essential oils of aromatic plants of different species, obtained from semisynthesis of citronellal, and is widely used as a fragrance in cosmetics. The objective of this work was to evaluate the possible anxiolytic-like activity of HC and its possible mechanism of action using in vivo and in silico methodologies. Swiss male mice (Mus musculus) were treated with HC (12.5, 25, and 50 mg/kg, i.p.) and subjected to the rota rod, elevated plus maze, and open field tests. No significant impairments were observed in the rota rod tests for the motor activity of the animals treated with HC at 12.5, 25, and 50 mg/kg, i.p., indicating no myo-relaxing or sedative effects. In the elevated plus maze, HC (in the three doses) induced significant increases in the percentage of entries (respectively, 34.8%, 33.8%, and 38.6%) and in the length of stay (respectively, 49.9%, 56.1%, and 57.0%) in the open arms of the EPM, as well as the number of crossings in the open field tests. The mechanism of action of the compound’s anxiolytic-like activity can be attributed to the involvement of GABAA receptors, and this interaction was observed in in vivo and in silico studies. For HC, the results suggest anxiolytic-like effects, possibly via modulation of the GABAergic system. The use of natural products to treat anxiety can become an alternative to existing synthetic products.

scholarly journals Antifungal Activity of N-(4-Halobenzyl)amides against Candida spp. and Molecular Modeling Studies

2021 ◽  
Vol 23 (1) ◽  
pp. 419
Author(s):  
Yunierkis Perez-Castillo ◽  
Ricardo Carneiro Montes ◽  
Cecília Rocha da Silva ◽  
João Batista de Andrade Neto ◽  
Celidarque da Silva Dias ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Benzoic Acid ◽  
Mechanism Of Action ◽  
Fungal Infections ◽  
Redox Balance ◽  
Inhibitory Effect ◽  
Candida Spp ◽  
Cellular Processes ◽  
Antifungal Action ◽  
Dynamics Simulations

Fungal infections remain a high-incidence worldwide health problem that is aggravated by limited therapeutic options and the emergence of drug-resistant strains. Cinnamic and benzoic acid amides have previously shown bioactivity against different species belonging to the Candida genus. Here, 20 cinnamic and benzoic acid amides were synthesized and tested for inhibition of C. krusei ATCC 14243 and C. parapsilosis ATCC 22019. Five compounds inhibited the Candida strains tested, with compound 16 (MIC = 7.8 µg/mL) producing stronger antifungal activity than fluconazole (MIC = 16 µg/mL) against C. krusei ATCC 14243. It was also tested against eight Candida strains, including five clinical strains resistant to fluconazole, and showed an inhibitory effect against all strains tested (MIC = 85.3–341.3 µg/mL). The MIC value against C. krusei ATCC 6258 was 85.3 mcg/mL, while against C. krusei ATCC 14243, it was 10.9 times smaller. This strain had greater sensitivity to the antifungal action of compound 16. The inhibition of C. krusei ATCC 14243 and C. parapsilosis ATCC 22019 was also achieved by compounds 2, 9, 12, 14 and 15. Computational experiments combining target fishing, molecular docking and molecular dynamics simulations were performed to study the potential mechanism of action of compound 16 against C. krusei. From these, a multi-target mechanism of action is proposed for this compound that involves proteins related to critical cellular processes such as the redox balance, kinases-mediated signaling, protein folding and cell wall synthesis. The modeling results might guide future experiments focusing on the wet-lab investigation of the mechanism of action of this series of compounds, as well as on the optimization of their inhibitory potency.

scholarly journals Derivatives of the antimalarial drug mefloquine are broad spectrum antifungal molecules with activity against drug-resistant clinical isolates

2019 ◽  
Author(s):  
Marhiah C. Montoya ◽  
Sarah Beattie ◽  
Kathryn M. Alden ◽  
Damian J. Krysan
Keyword(s):  
Antifungal Activity ◽  
Mechanism Of Action ◽  
Broad Spectrum ◽  
Fungal Infections ◽  
Clinical Isolates ◽  
In Vitro Toxicity ◽  
Drug Resistant ◽  
Candida Auris ◽  
Recent Emergence ◽  
Derivatives Of

ABSTRACTThe antifungal pharmacopeia is critically small, particularly in light of the recent emergence of multi-drug-resistant pathogens such as Candida auris. Herein, we report that derivatives of the anti-malarial drug mefloquine have broad spectrum antifungal activity against pathogenic yeasts and molds. In addition, the mefloquine derivatives have activity against clinical isolates that are resistant to one or more of the three classes of drugs currently used to treat invasive fungal infections, indicating that they have a novel mechanism of action. Importantly, the in vitro toxicity profiles using human cell lines indicate that the mefloquine derivatives are very similar to the parent mefloquine despite being up to 64-fold more active against fungal cells. In addition to direct antifungal activity, sub-inhibitory concentrations of the mefloquine derivatives inhibit the expression of virulence traits including filamentation in C. albicans and capsule formation/melanization in C. neoformans. Mode/mechanism of action experiments indicate that the mefloquine derivatives interfere with both mitochondrial and vacuolar function as part of a multi-target mechanism of action. The broad-spectrum scope of activity, blood-brain-barrier penetration, and large number of previously synthesized analogs available combine to support the further optimization and development of the antifungal activity of this general class of drug-like molecules.

scholarly journals In Vitro Confirmation of Siramesine as a Novel Antifungal Agent with In Silico Lead Proposals of Structurally Related Antifungals

Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3504
Author(s):  
Josipa Vlainić ◽  
Ozren Jović ◽  
Ivan Kosalec ◽  
Oliver Vugrek ◽  
Rozelindra Čož-Rakovac ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Antifungal Agent ◽  
In Silico ◽  
Fungal Infections ◽  
Clinical Investigation ◽  
Fungal Resistance ◽  
Ergosterol Biosynthesis ◽  
Published Data ◽  
Slow Development

The limited number of medicinal products available to treat of fungal infections makes control of fungal pathogens problematic, especially since the number of fungal resistance incidents increases. Given the high costs and slow development of new antifungal treatment options, repurposing of already known compounds is one of the proposed strategies. The objective of this study was to perform in vitro experimental tests of already identified lead compounds in our previous in silico drug repurposing study, which had been conducted on the known Drugbank database using a seven-step procedure which includes machine learning and molecular docking. This study identifies siramesine as a novel antifungal agent. This novel indication was confirmed through in vitro testing using several yeast species and one mold. The results showed susceptibility of Candida species to siramesine with MIC at concentration 12.5 µg/mL, whereas other candidates had no antifungal activity. Siramesine was also effective against in vitro biofilm formation and already formed biofilm was reduced following 24 h treatment with a MBEC range of 50–62.5 µg/mL. Siramesine is involved in modulation of ergosterol biosynthesis in vitro, which indicates it is a potential target for its antifungal activity. This implicates the possibility of siramesine repurposing, especially since there are already published data about nontoxicity. Following our in vitro results, we provide additional in depth in silico analysis of siramesine and compounds structurally similar to siramesine, providing an extended lead set for further preclinical and clinical investigation, which is needed to clearly define molecular targets and to elucidate its in vivo effectiveness as well.

scholarly journals Benzoquinoline Derivatives: A Straightforward and Efficient Route to Antibacterial and Antifungal Agents

2021 ◽  
Vol 14 (4) ◽  
pp. 335
Author(s):  
Vasilichia Antoci ◽  
Liliana Oniciuc ◽  
Dorina Amariucai-Mantu ◽  
Costel Moldoveanu ◽  
Violeta Mangalagiu ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Atp Synthase ◽  
In Silico ◽  
Cycloaddition Reaction ◽  
Biological Data ◽  
In Silico Admet ◽  
In Silico Studies ◽  
Topo Ii ◽  
Antibacterial And Antifungal ◽  
Best Fit

We report here the design, synthesis, experimental and in silico evaluation of the antibacterial and antifungal activity of some new benzo[f]quinoline derivatives. Two classes of benzo[f]quinolinium derivatives—(benzo[f]quinolinium salts (BQS) and pyrrolobenzo[f]quinolinium cycloadducts (PBQC)—were designed and obtained in two steps via a direct and facile procedure: quaternization followed by a cycloaddition reaction. The synthesized compounds were characterized by elemental and spectral analysis (FT-IR, 1H-NMR, 13C-NMR). The antimicrobial assay reveals that the BQS salts have an excellent quasi-nonselective antifungal activity against the fungus Candida albicans (some of them higher that the control drug nystatin) and very good antibacterial activity against the Gram positive bacterium Staphylococcus aureus. The PBQC compounds are inactive. Analysis of the biological data reveals interesting SAR correlations in the benzo[f]quinolinium series of compounds. The in silico studies furnished important data concerning the pharmacodynamics, pharmacokinetics and ADMET parameters of the BQS salts. Studies of the interaction of each BQS salt 3a–o with ATP synthase in the formed complex, reveal that salts 3j, 3i, and 3n have the best fit in a complex with ATP synthase. Study of the interaction of each BQS salt 3a-o with TOPO II in the formed complex reveals that salts 3j and 3n have the best-fit in complex with TOPO II. The in silico ADMET studies reveal that the BQS salts have excellent drug-like properties, including a low toxicity profile. Overall, the experimental and in silico studies indicate that compounds 3e and 3f (from the aliphatic series), respectively, and 3i, 3j and 3n (from the aromatic series), are promising leading drug candidates.

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