Ruthenium based antifungal compounds and their activity

2021 ◽  
Vol 25 (7) ◽  
pp. 177-182
Author(s):  
Rahul Kanaoujiya ◽  
Shekhar Srivastava
Keyword(s):  
Antifungal Activity ◽  
Drug Design ◽  
Ruthenium Complexes ◽  
Chemical Properties ◽  
Antifungal Drugs ◽  
Antifungal Drug ◽  
Attractive Alternative ◽  
Antifungal Compounds ◽  
Lower Toxicity ◽  
Ruthenium Compounds

Ruthenium is recognized as a highly attractive alternative to platinum since the toxicity of many ruthenium compounds is lower and some complexes are quite selective for antifungal drugs. Ruthenium has various chemical properties these chemical properties are very useful for antifungal drug design. Ruthenium compounds have several types of advantages as antifungal drugs because of lower toxicity. . Ruthenium has unique properties making it of particularly use as fungal in drug design specially in antifungal drugs. Several types of ruthenium complexes and their antifungal activity standards are described here.

scholarly journals High Efficiency Drug Repurposing Design for New Antifungal Agents

2019 ◽  
Vol 2 (2) ◽  
pp. 31 ◽  
Author(s):  
Jong H. Kim ◽  
Kathleen L. Chan ◽  
Luisa W. Cheng ◽  
Lisa A. Tell ◽  
Barbara A. Byrne ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Fungal Pathogens ◽  
Antifungal Agents ◽  
High Efficiency ◽  
Intervention Strategy ◽  
Drug Repurposing ◽  
Antifungal Drugs ◽  
Antifungal Drug ◽  
Alternative Intervention ◽  
Combined Application

Current antifungal interventions have often limited efficiency in treating fungal pathogens, particularly those resistant to commercial drugs or fungicides. Antifungal drug repurposing is an alternative intervention strategy, whereby new utility of various marketed, non-antifungal drugs could be repositioned as novel antifungal agents. In this study, we investigated “chemosensitization” as a method to improve the efficiency of antifungal drug repurposing, wherein combined application of a second compound (viz., chemosensitizer) with a conventional, non-antifungal drug could greatly enhance the antifungal activity of the co-applied drug. Redox-active natural compounds or structural derivatives, such as thymol (2-isopropyl-5-methylphenol), 4-isopropyl-3-methylphenol, or 3,5-dimethoxybenzaldehyde, could serve as potent chemosensitizers to enhance antifungal activity of the repurposed drug bithionol. Of note, inclusion of fungal mutants, such as antioxidant mutants, could also facilitate drug repurposing efficiency, which is reflected in the enhancement of antifungal efficacy of bithionol. Bithionol overcame antifungal (viz., fludioxonil) tolerance of the antioxidant mutants of the human/animal pathogen Aspergillus fumigatus. Altogether, our strategy can lead to the development of a high efficiency drug repurposing design, which enhances the susceptibility of pathogens to drugs, reduces time and costs for new antifungal development, and abates drug or fungicide resistance.

scholarly journals Chemical genetic analyses of compounds derived from feijoa fruit

2021 ◽  
Author(s):  
◽  
Mona Mokhtari
Keyword(s):  
Antifungal Activity ◽  
Mechanism Of Action ◽  
Antifungal Drugs ◽  
Chemical Diversity ◽  
Zinc Homeostasis ◽  
Genetic Profile ◽  
Antifungal Compounds ◽  
Genetic Analyses ◽  
Antifungal Mechanism ◽  
Chemical Genetic

<p>Nature has been a rich source of pharmaceutical compounds, producing 80% of our currently prescribed drugs. The feijoa plant, Acca sellowiana, is classified in the family Myrtaceae, native to South America, and currently grown worldwide to produce feijoa fruit. Compounds with anticancer, anti-inflammatory, antibacterial and antifungal activities have been isolated from feijoa; however, the diversity of these compounds is not known nor is the mechanism of action of any of these compounds. I hypothesized that identifying compounds in novel feijoa cultivars would improve our understanding of the chemical diversity of antifungal compounds in feijoa and determining the antifungal mechanism of action of feijoa compounds would provide insight into the pharmaceutical potential of these compounds. First, GC-MS analyses were used to obtain an unbiased profile of 151 compounds from 16 cultivars of feijoa, of which six were novel cultivars. Multivariate analysis distinguished 18 compounds that were significantly and positively correlated to antifungal activity based on growth inhibition of Saccharomyces cerevisiae, of which seven had not previously been described from feijoa. Two novel cultivars were identified as the most bioactive cultivars, and the compound 4-cyclopentene-1,3-dione found in a couple of cultivars was potently antifungal against human pathogenic isolates of four Candida species. Second, chemical genetic analyses were used to investigate the mechanism of action of estragole, an antifungal compound previously isolated from feijoa. The chemical genetic profile of estragole was distinct from that of other known antifungal compounds, suggesting the mechanism of action of estragole has a novel antifungal mechanism. Third, chemical genetic analyses were used to investigate the mechanism of action of an ethanol adduct of vescalagin (EtOH-vescalagin) isolated from feijoa. We showed EtOH-vescalagin is antifungal against human pathogenic strains. Genome-wide chemical genetic analyses of EtOH-vescalagin indicated antifungal activity is mediated by disruptions of iron homeostasis, zinc homeostasis and retromer recycling through iron chelation. Overall, these results indicate the chemical and biological value of feijoa as a source of antifungal drugs.</p>

scholarly journals Chemical genetic analyses of compounds derived from feijoa fruit

2021 ◽  
Author(s):  
◽  
Mona Mokhtari
Keyword(s):  
Antifungal Activity ◽  
Mechanism Of Action ◽  
Antifungal Drugs ◽  
Chemical Diversity ◽  
Zinc Homeostasis ◽  
Genetic Profile ◽  
Antifungal Compounds ◽  
Genetic Analyses ◽  
Antifungal Mechanism ◽  
Chemical Genetic

<p>Nature has been a rich source of pharmaceutical compounds, producing 80% of our currently prescribed drugs. The feijoa plant, Acca sellowiana, is classified in the family Myrtaceae, native to South America, and currently grown worldwide to produce feijoa fruit. Compounds with anticancer, anti-inflammatory, antibacterial and antifungal activities have been isolated from feijoa; however, the diversity of these compounds is not known nor is the mechanism of action of any of these compounds. I hypothesized that identifying compounds in novel feijoa cultivars would improve our understanding of the chemical diversity of antifungal compounds in feijoa and determining the antifungal mechanism of action of feijoa compounds would provide insight into the pharmaceutical potential of these compounds. First, GC-MS analyses were used to obtain an unbiased profile of 151 compounds from 16 cultivars of feijoa, of which six were novel cultivars. Multivariate analysis distinguished 18 compounds that were significantly and positively correlated to antifungal activity based on growth inhibition of Saccharomyces cerevisiae, of which seven had not previously been described from feijoa. Two novel cultivars were identified as the most bioactive cultivars, and the compound 4-cyclopentene-1,3-dione found in a couple of cultivars was potently antifungal against human pathogenic isolates of four Candida species. Second, chemical genetic analyses were used to investigate the mechanism of action of estragole, an antifungal compound previously isolated from feijoa. The chemical genetic profile of estragole was distinct from that of other known antifungal compounds, suggesting the mechanism of action of estragole has a novel antifungal mechanism. Third, chemical genetic analyses were used to investigate the mechanism of action of an ethanol adduct of vescalagin (EtOH-vescalagin) isolated from feijoa. We showed EtOH-vescalagin is antifungal against human pathogenic strains. Genome-wide chemical genetic analyses of EtOH-vescalagin indicated antifungal activity is mediated by disruptions of iron homeostasis, zinc homeostasis and retromer recycling through iron chelation. Overall, these results indicate the chemical and biological value of feijoa as a source of antifungal drugs.</p>

scholarly journals Antifungal Drug Development: Targeting the Fungal Sphingolipid Pathway

2020 ◽  
Vol 6 (3) ◽  
pp. 142
Author(s):  
Kyle McEvoy ◽  
Tyler G. Normile ◽  
Maurizio Del Poeta
Keyword(s):  
Drug Resistance ◽  
Drug Development ◽  
Mechanism Of Action ◽  
Fungal Infections ◽  
Antifungal Drugs ◽  
Antifungal Drug ◽  
Antifungal Compounds ◽  
Metabolizing Enzymes ◽  
Progressive Development

Fungal infections are becoming more prevalent and problematic due to the continual rise of immune deficient patients as well as the progressive development of drug resistance towards currently available antifungal drugs. There has been a significant increase in the development of antifungal compounds with a similar mechanism of action of current drugs. In contrast, there has been very little progress in developing compounds inhibiting totally new fungal targets or/and fungal pathways. This review focuses on novel compounds recently discovered to target the fungal sphingolipids and their metabolizing enzymes.

Antifungal activity of rare actinobacterium isolated from forest soil

2021 ◽  
Vol 16 (10) ◽  
pp. 92-101
Author(s):  
Muralidharan Sasidhar ◽  
Selvam Masilamani ◽  
Abirami Baskaran ◽  
Manigundan Kaari ◽  
Radhakrishnan Manikkam
Keyword(s):  
Antifungal Activity ◽  
Forest Soil ◽  
Fungal Pathogens ◽  
Antifungal Agents ◽  
Carbon Sources ◽  
Nitrogen Sources ◽  
Antifungal Drugs ◽  
Antifungal Compound ◽  
Antifungal Compounds ◽  
Promising Source

Prolonged use of antifungal drugs has led to the emergence of drug resistant fungal pathogens that pose serious threat to public health and challenge to researchers for discovering novel antifungal agents. Natural products from the members of phylum actinobacteria are the promising source of antibiotics including antifungal agents. Twenty-seven morphologically different actinobacterial cultures were isolated from the forest soils of Sabarimala, Kerala and Lucknow, Uttar Pradesh. Actinobacterial strain LA34 showed promising antifungal activity when screened against Candida albicans and Cryptococcus neoformans, hence selected as potential strain. Antifungal compounds were produced from the strain LA34 using agar surface fermentation and its extraction was done using ethyl acetate and methanol. Results of cultural, microscopic and physiological characteristics as well as cell wall amino acid and sugars analysis revealed that the strain LA34 was nonstreptomyces or rare actinobacterium. Various carbon sources, nitrogen sources and minerals were found to influence antifungal compound production by the strain LA34. The present study concluded that the rare actinobacterial strain LA34 isolated from Lucknow forest soil is a promising source for the isolation of antifungal compounds.

scholarly journals In Vitro and In Vivo Assessment of FK506 Analogs as Novel Antifungal Drug Candidates

2018 ◽  
Vol 62 (11) ◽  
Author(s):  
Yeonseon Lee ◽  
Kyung-Tae Lee ◽  
Soo Jung Lee ◽  
Ji Yoon Beom ◽  
Areum Hwangbo ◽  
...  
Keyword(s):  
Antifungal Activity ◽  
Pathogenic Fungi ◽  
Antifungal Drugs ◽  
Antifungal Drug ◽  
Immunosuppressive Activity ◽  
Activated T Cells ◽  
Content Type ◽  
Antifungal Efficacy

ABSTRACT FK506 (tacrolimus) is an FDA-approved immunosuppressant indicated for the prevention of allograft rejections in patients undergoing organ transplants. In mammals, FK506 inhibits the calcineurin-nuclear factor of activated T cells (NFAT) pathway to prevent T-cell proliferation by forming a ternary complex with its binding protein, FKBP12, and calcineurin. FK506 also exerts antifungal activity by inhibiting calcineurin, which is essential for the virulence of human-pathogenic fungi. Nevertheless, FK506 cannot be used directly as an antifungal drug due to its immunosuppressive action. In this study, we analyzed the cytotoxicity, immunosuppressive activity, and antifungal activity of four FK506 analogs, 31-O-demethyl-FK506, 9-deoxo-FK506, 9-deoxo-31-O-demethyl-FK506, and 9-deoxo-prolyl-FK506, in comparison with that of FK506. The four FK506 analogs generally possessed lower cytotoxicity and immunosuppressive activity than FK506. The FK506 analogs, except for 9-deoxo-prolyl-FK506, had strong antifungal activity against Cryptococcus neoformans and Candida albicans, which are two major invasive pathogenic yeasts, due to the inhibition of the calcineurin pathway. Furthermore, the FK506 analogs, except for 9-deoxo-prolyl-FK506, had strong antifungal activity against the invasive filamentous fungus Aspergillus fumigatus. Notably, 9-deoxo-31-O-demethyl-FK506 and 31-O-demethyl-FK506 exhibited robust synergistic antifungal activity with fluconazole, similar to FK506. Considering the antifungal efficacy, cytotoxicity, immunosuppressive activity, and synergistic effect with commercial antifungal drugs, we selected 9-deoxo-31-O-demethyl-FK506 for further evaluation of its in vivo antifungal efficacy in a murine model of systemic cryptococcosis. Although 9-deoxo-31-O-demethyl-FK506 alone was not sufficient to treat the cryptococcal infection, when it was used in combination with fluconazole, it significantly extended the survival of C. neoformans-infected mice, confirming the synergistic in vivo antifungal efficacy between these two agents.

Efficacy of Novel Schiff base Derivatives as Antifungal Compounds in Combination with Approved Drugs Against Candida Albicans

2019 ◽  
Vol 15 (6) ◽  
pp. 648-658 ◽  
Author(s):  
Manzoor Ahmad Malik ◽  
Shabir Ahmad Lone ◽  
Parveez Gull ◽  
Ovas Ahmad Dar ◽  
Mohmmad Younus Wani ◽  
...  
Keyword(s):  
Schiff Base ◽  
Candida Albicans ◽  
Antifungal Activity ◽  
Fungal Infections ◽  
Total Sterol ◽  
Antifungal Drugs ◽  
New Drugs ◽  
Ergosterol Biosynthesis ◽  
Dependent Manner ◽  
Schiff Base Derivatives

Background: The increasing incidence of fungal infections, especially caused by Candida albicans, and their increasing drug resistance has drastically increased in recent years. Therefore, not only new drugs but also alternative treatment strategies are promptly required. Methods: We previously reported on the synergistic interaction of some azole and non-azole compounds with fluconazole for combination antifungal therapy. In this study, we synthesized some non-azole Schiff-base derivatives and evaluated their antifungal activity profile alone and in combination with the most commonly used antifungal drugs- fluconazole (FLC) and amphotericin B (AmB) against four drug susceptible, three FLC resistant and three AmB resistant clinically isolated Candida albicans strains. To further analyze the mechanism of antifungal action of these compounds, we quantified total sterol contents in FLC-susceptible and resistant C. albicans isolates. Results: A pyrimidine ring-containing derivative SB5 showed the most potent antifungal activity against all the tested strains. After combining these compounds with FLC and AmB, 76% combinations were either synergistic or additive while as the rest of the combinations were indifferent. Interestingly, none of the combinations was antagonistic, either with FLC or AmB. Results interpreted from fractional inhibitory concentration index (FICI) and isobolograms revealed 4-10-fold reduction in MIC values for synergistic combinations. These compounds also inhibit ergosterol biosynthesis in a concentration-dependent manner, supported by the results from docking studies. Conclusion: The results of the studies conducted advocate the potential of these compounds as new antifungal drugs. However, further studies are required to understand the other mechanisms and in vivo efficacy and toxicity of these compounds.

scholarly journals Expression of Ubiquitin Gene in Microsporum canis and Trichophyton mentagrophytes Cultured with Fluconazole

2001 ◽  
Vol 45 (9) ◽  
pp. 2559-2562 ◽  
Author(s):  
Rui Kano ◽  
Ken Okabayashi ◽  
Yuka Nakamura ◽  
Shinichi Watanabe ◽  
Atsuhiko Hasegawa
Keyword(s):  
Amino Acid ◽  
Antifungal Activity ◽  
Proteasome Inhibitor ◽  
Trichophyton Mentagrophytes ◽  
Nucleotide Sequences ◽  
Amino Acid Sequences ◽  
Antifungal Drug ◽  
Microsporum Canis

ABSTRACT The expression of the ubiquitin (Ub) gene in dermatophytes was examined for its relation to resistance against the antifungal drug fluconazole. The nucleotide sequences and the deduced amino acid sequences of the Ub gene in Microsporum canis were proven to be 99% similar to those of the Ub gene in Trichophyton mentagrophytes. Expression of mRNA of Ub in M. canisand T. mentagrophytes was enhanced when the fungi were cultured with fluconazole. The antifungal activity of fluconazole against these dermatophytes was increased in the presence of Ub proteasome inhibitor.

Biosynthesis of selenium nanoparticles by Aspergillus flavus and Candida albicans and comparison of their effects with antifungal drugs

2021 ◽  
Author(s):  
Mahdi Hosseini Bafghi ◽  
Razieh Nazari ◽  
Majid Darroudi ◽  
Mohsen Zargar ◽  
Hossein Zarrinfar
Keyword(s):  
Candida Albicans ◽  
Aspergillus Flavus ◽  
Fungal Pathogens ◽  
Chemical Properties ◽  
Cost Effective ◽  
Antifungal Drugs ◽  
Selenium Nanoparticles ◽  
Fungal Strains ◽  
Vis Spectroscopy ◽  
Physical And Chemical

Abstract Biosynthesis of nanoparticles can stand as a replacement for the available chemical and physical methods by offering new procedures as green syntheses that have proved to be simple, biocompatible, safe, and cost-effective. Considering how nanoparticles with a size of 1 to 100 nanometers contain unique physical and chemical properties, recent reports are indicative of observing the antifungal qualities of selenium nanoparticles (Se-NPs). Recently, the observance of antifungal resistance towards different species of these fungi is often reported. Therefore, due to the antifungal effects of biological nanoparticles, this study aimed to investigate the exertion of these nanoparticles and evaluate their effects on the growth of fungal pathogens. Se-NPs were biosynthesized by the application of wet reduction method, which included specific concentrations of Aspergillus flavus and Candida albicans. The presence of nanoparticles was confirmed by methods such as UV-Vis spectroscopy, FT-IR analysis, and FESEM electron microscope that involved FESEM and EDAX diagram. The fungal strains were cultured in sabouraud dextrose agar medium to perform the sensitivity test based on the minimum inhibitory concentration (MIC) method in duplicate. The utilization of Se-NPs at concentrations of 1 µg/ ml and below resulted in zero growth of fungal agents. However, their growth was inhibited by antifungal drugs at concentrations of 2 µg/ ml and higher. Based on the obtained results, biological nanoparticles produced by fungal agents at different concentrations exhibited favorable inhibitory effects on the growth of fungal strains.

GROWTH INHIBITORY ACTIVITIES OF THE RHIZOME CRUDE EXTRACT OF Curcuma longa ON THE HUMAN PATHOGENIC FUNGUS Mucor circinelloides

2020 ◽  
Vol 65 (10) ◽  
pp. 82-91
Author(s):  
Phuong Nguyen Anh ◽  
Mai Le Thi Tuyet ◽  
Trung Trieu Anh
Keyword(s):  
Antifungal Activity ◽  
Crude Extract ◽  
Fungal Infections ◽  
Early Stage ◽  
Curcuma Longa ◽  
Pathogenic Fungus ◽  
Mucor Circinelloides ◽  
Antifungal Drugs ◽  
Diffusion Method ◽  
Dilution Method

Mucormycosis is an uncommon but life-threatening invasive fungal infection, mostly occurs in immunocompromised patients. Lacking the appropriate antifungal drugs is one of the reasons that lead to difficulties in the management of mucormycosis. Curcuma longa has been used traditionally and widely to treat various diseases, including fungal infections. In the search for novel antifungal compounds from natural resources, we evaluated the effect of rhizome crude extract of C. longa on Mucor circinelloides – a causal agent of mucormycosis. The results of screening, using broth dilution method and agar-well diffusion method, showed that the C. longa extract exhibited promising antifungal activity against the fungus M. circinelloides. In liquid medium, C. longa extract decreased the ability of spore germination and the speed of hyphae formation of M. circinelloides decreased by up to approximately 70% and 90%, respectively. Besides, in a solid medium, the crude extract presented similar activity with amphotericin B (400 μg\mL) in decreasing the growth of M. circinelloides by nearly 77%. Moreover, the extract of C. longa also likely to induce the yeast-like type of growth of the dimorphic M. circinelloides in the early stage. These results suggest the plant could be a potential source for further study on biochemical components and the mechanism of its antifungal activity.

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