Antifungal Activity of Linear and Disulfide-Cyclized Ultrashort Cationic Lipopeptides Alone and in Combination with Fluconazole Against Vulvovaginal Candida spp.

Abstract Vulvovaginal candidiasis (VVC) occurs in over 75% of women at least once during their lifetime and is an infection that significantly affects their health. Candida strains resistant to standard azole antifungal therapy and relapses of VVC are more and more common. Hypothetically, biofilm is one of the main reasons of relapses and failure of the therapy. Ultrashort cationic lipopeptides (USCLs) exhibit high antimicrobial activities. Our previous study on USCLs revealed that disulfide cyclization can result in selective antifungal compounds. Therefore, four USCL were selected and their antifungal activity were studied on 62 clinical strains isolated from VVC. The results showed that cyclic analogs have increased selectivity between fungal cells and keratinocytes and improved anticandidal activity than their linear analogs against both planktonic and biofilm cultures. On the other hand, linear lipopeptides in combination with fluconazole showed the synergistic effect. It was found that the minimum inhibitory concentrations of the tested compounds in combination with fluconazole were at least four times lower than when used separately. Our results indicate that combination therapy of VVC with USCLs and fluconazole at low non-toxic concentrations can be beneficial owing to the synergistic effect. However, further in vivo studies are needed to confirm this hypothesis.

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Antifungal Activity of Linear and Disulfide-Cyclized Ultrashort Cationic Lipopeptides Alone and in Combination with Fluconazole against Vulvovaginal Candida spp.

Pharmaceutics ◽

10.3390/pharmaceutics13101589 ◽

2021 ◽

Vol 13 (10) ◽

pp. 1589

Author(s):

Paulina Czechowicz ◽

Damian Neubauer ◽

Joanna Nowicka ◽

Wojciech Kamysz ◽

Grażyna Gościniak

Keyword(s):

Antifungal Activity ◽

Synergistic Effect ◽

Antimicrobial Activities ◽

The Other ◽

In Vivo Studies ◽

Antifungal Compounds ◽

Candida Spp ◽

Anticandidal Activity ◽

Toxic Concentrations

Vulvovaginal candidiasis (VVC) occurs in over 75% of women at least once during their lifetime and is an infection that significantly affects their health. Candida strains resistant to standard azole antifungal therapy and relapses of VVC are more and more common. Hypothetically, biofilm is one of the main reasons of relapses and failure of the therapy. Ultrashort cationic lipopeptides (USCLs) exhibit high antimicrobial activities. Our previous study on USCLs revealed that disulfide cyclization can result in selective antifungal compounds. Therefore, four USCL were selected and their antifungal activity were studied on 62 clinical strains isolated from VVC. The results confirmed previous premises that cyclic analogs have increased selectivity between fungal cells and keratinocytes and improved anticandidal activity compared to their linear analogs against both planktonic and biofilm cultures. On the other hand, linear lipopeptides in combination with fluconazole showed a synergistic effect. It was found that the minimum inhibitory concentrations of the tested compounds in combination with fluconazole were at least four times lower than when used separately. Our results indicate that combination therapy of VVC with USCLs and fluconazole at low non-toxic concentrations can be beneficial owing to the synergistic effect. However, further in vivo studies are needed to confirm this hypothesis.

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Induction of antimicrobial peptides from Rana dybowskii under Rana grylio virus stress, and bioactivity analysis

Canadian Journal of Microbiology ◽

10.1139/w2012-055 ◽

2012 ◽

Vol 58 (7) ◽

pp. 848-855 ◽

Cited By ~ 7

Author(s):

Shu-Jing Yang ◽

Xiang-Hong Xiao ◽

Yi-Gang Xu ◽

Dan-Dan Li ◽

Long-Hui Chai ◽

...

Keyword(s):

Antimicrobial Peptides ◽

Antimicrobial Activities ◽

The Other ◽

Degenerate Primers ◽

Cdna Sequences ◽

Gram Positive Bacteria ◽

Pathogen Invasion ◽

Peptide Precursors ◽

Rana Dybowskii

The skin glands of Ranidae are a rich source of antimicrobial peptides. In this study, the genomic RNA of Rana dybowskii was extracted from its skin while under Rana grylio virus stress. Five new cDNA sequences encoding 5 mature peptides, Ranatuerin-2YJ (GLMDIFKVAVNKLLAAGMNKPRCKAAHC), Dybowskin-YJb (IIPLPLGYFAKKP), Dybowskin-YJa (IIPLPLGYFAKKKKKKDPVPLDQ), Temperin-YJa (VLPLLETCSMTCWENNQTFGK), and Temperin-YJb (VLPLVGNLLNDLLGK), were obtained by reverse transcription polymerase chain reaction with a pair of degenerate primers designed according to the conserved terminal sequences of cDNA encoding antimicrobial peptide precursors of genus Rana. The antimicrobial activities of the peptides were analyzed, and the results demonstrated that all these peptides showed a significant anti-Rana grylio virus activity, and the virus was gradually cleared with the increase in gene expression. Among the 5 peptides obtained in this work, Ranatuerin-2YJ also showed a broad-spectrum anti-Gram-positive bacteria and anti-Gram-negative bacteria activity with a minimal inhibitory concentration of 22.5 µg/mL and 7.64% hemolysis activity, both of which were significantly lower (p < 0.05) than that of the other peptides. Moreover, Ranatuerin-2YJ was widely distributed in the skin, liver, spleen, and blood of R. dybowskii, while the other 4 peptides could only be cloned from the skin, indicating that the Ranatuerin-2YJ in vivo plays an important role in the protection against pathogen invasion.

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Synthesis and Evaluation of Bioactivity of 6-[(2-Pyridinyloxy)](Benzo)Imidazo[2,1-b][1,3]Thiazine Derivatives

Biointerface Research in Applied Chemistry ◽

10.33263/briac124.50315044 ◽

2021 ◽

Vol 12 (4) ◽

pp. 5031-5044

Keyword(s):

Antifungal Activity ◽

The Other ◽

Albino Rats ◽

Target Compound ◽

Mild Conditions ◽

In Vivo Experiments ◽

Nmr Spectrometry ◽

Suppression Index

A series of new 6-[(pyridine-2-yl)oxy]-6,7-dihydro-5H-imidazo[2,1-b]thiazines 4a-l and their benzoannelated derivatives 4m-r was synthesized by the reaction between 3-hydroxy(benzo)imidazo[2,1-b][1,3]thiazines and substituted 2-chloropyridines under the mild conditions with the yield 53-74 %. The structure of the target compound was proven by the results of 1H NMR, 13C NMR spectrometry, and LC-MS. In silico evaluation of these drug-like compounds proved that many of them comply with the Lipinski ‘rule of five’ and the Veber rule. Antibacterial, antifungal, and anti-inflammatory activity of all synthesized compounds were investigated in the in vitro and in vivo experiments. According to the bio screening results, the compounds 6-[(5-сhloropyridin-2-yl)oxy]-6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazine 4a, 6-[(3,5-dichloropyridin-2-yl)oxy]-6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazine 4e and 6-{[3-chloro-5-(trifluoromethyl)pyridin-2-yl]oxy}-2,3-diphenyl-6,7-dihydro-5H-imidazo[2,1-b][1,3]thiazine 4l proved antifungal activity against Candida albicans. On the other hand, 3-[(3,5-dichloropyridin-2-yl)oxy]-3,4-dihydro-2H-benzo[4,5]imidazo[2,1-b][1,3]thiazine 4q proved the best antifungal activity against Aspergillus niger K 9 (MIC=15.62 µg/ml) and comparatively high antiedema activity against the carrageenan-induced edema of the hind paws of albino rats (the inflammation suppression index was 39.1 %).

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Synergistic anticandidal activity of etomidate and azoles against clinical fluconazole-resistant Candida isolates

Future Microbiology ◽

10.2217/fmb-2019-0075 ◽

2019 ◽

Vol 14 (17) ◽

pp. 1477-1488 ◽

Cited By ~ 4

Author(s):

Lívia G do AV Sá ◽

Cecília R da Silva ◽

Rosana de S Campos ◽

João B de A Neto ◽

Letícia S Sampaio ◽

...

Keyword(s):

Antifungal Activity ◽

Antifungal Drugs ◽

Planktonic Cells ◽

Candida Spp ◽

Flow Cytometric ◽

Fluconazole Resistant ◽

Anticandidal Activity ◽

Checkerboard Assay ◽

Resistant Strains ◽

Radical Generation

Aim: The purpose of this study was to evaluate the effect of etomidate alone and in combination with azoles on resistant strains of Candida spp. in both planktonic cells and biofilms. Materials & methods: The antifungal activity of etomidate was assessed by the broth microdilution test; flow cytometric procedures to measure fungal viability, mitochondrial transmembrane potential, free radical generation and cell death; as well detection of DNA damage using the comet assay. The interaction between etomidate and antifungal drugs (itraconazole and fluconazole) was evaluated by the checkerboard assay. Results: Etomidate showed antifungal activity against resistant strains of Candida spp. in planktonic cells and biofilms. Etomidate also presented synergism with fluconazole and itraconazole in planktonic cells and biofilms. Conclusion: Etomidate showed antifungal activity against Candida spp., indicating that it is a possible therapeutic alternative.

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Phytochemical composition, antifungal activity, in vitro and in vivo toxicity of Syzygium cumini (L.) Skeels leaves extract

Boletin Latinoamericano y del Caribe de Plantas Medicinales y Aromaticas ◽

10.37360/blacpma.21.20.5.40 ◽

2021 ◽

Vol 20 (5) ◽

pp. 536-555

Author(s):

Ernani Canuto Figueiredo Junior ◽

◽

Yuri Wanderley Cavalcanti ◽

Andressa Brito Lira ◽

Hilzeth de Luna Freire Pessoa ◽

...

Keyword(s):

Antioxidant Activity ◽

Antifungal Activity ◽

Galleria Mellonella ◽

In Vitro Assays ◽

Syzygium Cumini ◽

Candida Spp ◽

In Vivo Toxicity ◽

Phytochemical Composition

This study determined phytochemical composition, antifungal activity and toxicity in vitro and in vivo of Syzygium cumini leaves extract (Sc). Thus, was characterized by gas chromatography coupled to mass spectrometry and submitted to determination of Minimum Inhibitory (MIC) and Fungicidal concentrations (MFC) on reference and clinical strains of Candida spp. and by growth kinetics assays. Toxicity was verified using in vitro assays of hemolysis, osmotic fragility, oxidant and antioxidant activity in human erythrocytes and by in vivo acute systemic toxicity in Galleria mellonella larvae. Fourteen different compounds were identified in Sc, which showed antifungal activity (MIC between 31.25-125 μg/mL) with fungistatic effect on Candida. At antifungal concentrations, it demonstrated low cytotoxicity, antioxidant activity and neglible in vivo toxicity. Thus, Sc demonstrated a promising antifungal potential, with low toxicity, indicating that this extract can be a safe and effective alternative antifungal agent.

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The Effect of Curcumin and Cotrimoxazole in Salmonella Typhimurium Infection In Vivo

ISRN Microbiology ◽

10.1155/2013/601076 ◽

2013 ◽

Vol 2013 ◽

pp. 1-4 ◽

Cited By ~ 4

Author(s):

Siwipeni Irmawanti Rahayu ◽

Nurdiana Nurdiana ◽

Sanarto Santoso

Keyword(s):

Combination Therapy ◽

Antimicrobial Agent ◽

Typhoid Fever ◽

Salmonella Typhimurium ◽

Active Compound ◽

Adjunctive Therapy ◽

Antimicrobial Effect ◽

The Other ◽

Other Hand

Typhoid fever is a disease caused by Salmonella Typhi and commonly treated by an antimicrobial agent such as cotrimoxazole. On the other hand, herbal usage has risen as an adjunctive therapy to treat many diseases. Curcuma (Curcuma domestica) is a commonly used herb which consists of curcumin as its major active compound. Curcumin has been known for its antimicrobial effect, but there is no proof regarding the usage of curcumin and cotrimoxazole together. This research was conducted by using typhoid fever model in mice infected by Salmonella Typhimurium. Each animal was treated with curcumin, cotrimoxazole, or both. Ileum, spleen, and liver of each animal were isolated and cultured. We found that curcumin-cotrimoxazole combination therapy lowered the antimicrobial effectivity of cotrimoxazole in both intraintestinal and extraintestinal organs. We conclude that curcumin-cotrimoxazole combination therapy in typhoid fever has to be reconsidered.

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Effect of ozonized olive oil on oral levels of Candida spp. in patients with denture stomatitis

Brazilian Dental Science ◽

10.14295/bds.2018.v21i1.1489 ◽

2018 ◽

Vol 21 (1) ◽

pp. 111 ◽

Cited By ~ 1

Author(s):

Erica Crastechini ◽

Cristiane Yumi Koga-Ito ◽

Suzan De Fátima Machado ◽

Guilherme Rodrigues Teodoro ◽

Graziella Nuernberg Back-Brito ◽

...

Keyword(s):

Antifungal Activity ◽

Olive Oil ◽

In Vitro Tests ◽

Candida Spp ◽

Isolation And Identification ◽

Denture Stomatitis ◽

Viable Cells ◽

In Vitro Antifungal Activity

Objective: The aim of this study was to evaluate the effect of ozonized oil (OZ) on the oral levels of Candida spp. in patients with denture stomatitis. Material and Methods: In vitro tests were performed to validate antifungal activity and to standardize OZ conditions. Antifungal activity was screened against C. albicans and five non-albicans species (C. tropicalis, C. dubliniensis, C. krusei, C. guilliermondii, and C. parapsilosis). Also, the effects on C. albicans planktonic and biofilm were evaluated. After validation, OZ was included in a therapeutic protocol of denture stomatitis in vivo. Thirty patients used OZ and 20 used sodium bicarbonate (SB) for 14 days. After 7 and 14 days, clinical evaluation, isolation and identification of yeasts were performed. Isolates were identified by phenotypic and genotypic tests. Ozonized oil showed in vitro antifungal activity against all species of Candida. Ozonized oil reduced the number of viable cells in C. albicans biofilms. Oral candidal levels were lower in relation to baseline both after after 14 days of treatment with SB and OZ. Results: A total of 493 Candida spp. isolates was obtained and 80% were identified as C. albicans. Remission of denture stomatitis was observed in all patients after 7 days of treatment in both groups. Conclusion: Within the limits of the study we can conclude that ozonized olive oil can be a new alternative for the control of biofilm in patients with denture stomatitis. KeywordsOzone; Candida; Antifungal Agents; Stomatitis; Denture.

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EVALUATION OF ANTIFUNGAL AND ANTIBACTERIAL ACTIVITY OF SOME NEW BENZIMIDAZOLE DERIVATIVES

Latin American Applied Research - An international journal ◽

10.52292/j.laar.2018.270 ◽

2018 ◽

Vol 48 (2) ◽

pp. 125-129

Author(s):

K. ZOMORODIAN ◽

S. KHABNADIDEH ◽

L. ZAMANI ◽

K. PAKSHIR ◽

M. TAJADDOD

Keyword(s):

Antifungal Activity ◽

Fungal Infections ◽

Antimicrobial Activities ◽

Antifungal Drugs ◽

In Vivo Studies ◽

Benzimidazole Derivatives ◽

Dilution Method ◽

Gram Positive ◽

Meta Position

The extensive use of antifungal drugs and their resistance against fungal infections have led to discover new antimicrobial compounds. We previously described synthesis of some new derivatives of 2-methylbenzimidazole (1a-5a) and 5,6dimethylbenzimidazol (1b-5b). Here we evaluated the antimicrobial activities of these compounds against different species of micro organisms including gram positive and gram negative bacteria as well as fungi. Broth micro-dilution method as recommended by clinical and laboratory standard institute (CLSI) was used for this purpose. The results show compounds 2-Methyl-1-(3-methylbenzyl)-1H-benzo [d]imidazole (5a) and 5,6-Dimethyl-1-(3-methyl benzyl)-1H-benzo[d]imidazole (5b) had the best antifungal activity against the examined fungi and gram positive bacteria. Moreover these two compounds inhibited the growth of azole resistant strains. By comparison the relationship between the structures and activities of the tested compounds revealed that the presence of methyl residue in meta position of benzyl group enhance the antifungal activity. Regarding a broad spectrum antifungal activities of some of the tested compounds, they might be a good candidate for further in vivo studies to evaluate their pharmacological activity and toxicity as a novel antifungal agents.

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Synthesis, Biological Evaluation, and Structure–Activity Relationships of 4-Aminopiperidines as Novel Antifungal Agents Targeting Ergosterol Biosynthesis

Molecules ◽

10.3390/molecules26237208 ◽

2021 ◽

Vol 26 (23) ◽

pp. 7208

Author(s):

Jürgen Krauß ◽

Christoph Müller ◽

Monika Klimt ◽

Leandro Jorquera Valero ◽

José Francisco Martínez ◽

...

Keyword(s):

Antifungal Activity ◽

Galleria Mellonella ◽

Cholesterol Biosynthesis ◽

Biological Evaluation ◽

Ergosterol Biosynthesis ◽

In Vivo Model ◽

Candida Spp ◽

Mcf10a Cells

The aliphatic heterocycles piperidine and morpholine are core structures of well-known antifungals such as fenpropidin and fenpropimorph, commonly used as agrofungicides, and the related morpholine amorolfine is approved for the treatment of dermal mycoses in humans. Inspired by these lead structures, we describe here the synthesis and biological evaluation of 4-aminopiperidines as a novel chemotype of antifungals with remarkable antifungal activity. A library of more than 30 4-aminopiperidines was synthesized, starting from N-substituted 4-piperidone derivatives by reductive amination with appropriate amines using sodium triacetoxyborohydride. Antifungal activity was determined on the model strain Yarrowia lipolytica, and some compounds showed interesting growth-inhibiting activity. These compounds were tested on 20 clinically relevant fungal isolates (Aspergillus spp., Candida spp., Mucormycetes) by standardized microbroth dilution assays. Two of the six compounds, 1-benzyl-N-dodecylpiperidin-4-amine and N-dodecyl-1-phenethylpiperidin-4-amine, were identified as promising candidates for further development based on their in vitro antifungal activity against Candida spp. and Aspergillus spp. Antifungal activity was determined for 18 Aspergillus spp. and 19 Candida spp., and their impact on ergosterol and cholesterol biosynthesis was determined. Toxicity was determined on HL-60, HUVEC, and MCF10A cells, and in the alternative in vivo model Galleria mellonella. Analysis of sterol patterns after incubation gave valuable insights into the putative molecular mechanism of action, indicating inhibition of the enzymes sterol C14-reductase and sterol C8-isomerase in fungal ergosterol biosynthesis.

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