Tacrolimus as Antifungal Agent

Antypenko, Lyudmyla; Meyer, F.; Sadykova, Zhanar; Garbe, Leif‐Alexander; Steffens, Karl

doi:10.17344/acsi.2018.4723

Cited by 7 publications

(7 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Disulfiram, a drug inhibiting the aldehyde dehydrogenase (P05091) that is used to treat chronic alcoholism, showed strong inhibitory effects in Candida albicans and Candida auris [ 30 ]. The immunosuppressive drug tacrolimus, targeting the peptidyl-prolyl cis-trans isomerase FKBP1A (P62942) had effects in 11 fungi and 3 oomycetes of agricultural importance [ 31 ]. Finally, vorinostat, targeting histone deacetylases (Q92769, Q9UBN7) and used in the treatment of cutaneous T cell lymphomas, showed strong effects in Aspergillus spp.…”

Section: Resultsmentioning

confidence: 99%

Identifying Potential Molecular Targets in Fungi Based on (Dis)Similarities in Binding Site Architecture with Proteins of the Human Pharmacolome

et al. 2023

View full text Add to dashboard Cite

Invasive fungal infections represent a public health problem that worsens over the years with the increasing resistance to current antimycotic agents. Therefore, there is a compelling medical need of widening the antifungal drug repertoire, following different methods such as drug repositioning, identification and validation of new molecular targets and developing new inhibitors against these targets. In this work we developed a structure-based strategy for drug repositioning and new drug design, which can be applied to infectious fungi and other pathogens. Instead of applying the commonly accepted off-target criterion to discard fungal proteins with close homologues in humans, the core of our approach consists in identifying fungal proteins with active sites that are structurally similar, but preferably not identical to binding sites of proteins from the so-called “human pharmacolome”. Using structural information from thousands of human protein target-inhibitor complexes, we identified dozens of proteins in fungal species of the genera Histoplasma, Candida, Cryptococcus, Aspergillus and Fusarium, which might be exploited for drug repositioning and, more importantly, also for the design of new fungus-specific inhibitors. As a case study, we present the in vitro experiments performed with a set of selected inhibitors of the human mitogen-activated protein kinases 1/2 (MEK1/2), several of which showed a marked cytotoxic activity in different fungal species.

show abstract

Section: Resultsmentioning

confidence: 99%

Identifying Potential Molecular Targets in Fungi Based on (Dis)Similarities in Binding Site Architecture with Proteins of the Human Pharmacolome

et al. 2023

View full text Add to dashboard Cite

show abstract

“…The antitumor, antimicrobial, and fungicidal activity of S-substituted tetrazolo[1,5-c]quinazoline-5(6Н)-thiones were described by Antypenko et al 52,53 It was shown, that 2-(tetrazolo[1,5-с]quinazolin-5-ylsulfanyl)ethanones 100c-g ( Fig. 1) Compounds 100c-g revealed moderate antitumor activity against standard NCI lines panel (Fig.…”

Section: Biological Properties Of 2-thiopyrimidinesmentioning

confidence: 92%

“…The subsequent alkaline hydrolysis of compound 50 allowed to obtain 1,5-binucleophile 51 which was then transformed into ribosylpyrophosphate 2-mercapto-1,N 6 -ethenoadenosine diphosphate (52) via [5+1] heterocyclization with carbon disulfide. Alkylation of compound 52 by 3-bromopropanamine yielded the corresponding 2-[(3-aminopropyl)sulfanyl]-1,N 6 -ethenoadenosine diphosphate (53). Further degradation of the imidazole cycle by N-bromosuccinimide allowed to obtain 2-[(3-aminopropyl)sulfanyl]adenosine diphosphate (54).…”

Section: [5+1] Heterocyclizationmentioning

confidence: 99%

Preparation and biological properties of 2-thio-containing pyrimidines and their condensed analogs

Voskoboynik

Kolomoets

Берест

et al. 2017

Chem Heterocycl Comp

View full text Add to dashboard Cite

3+3] HeterocyclizationsAlthough the formation of 2-thioxo-or 2-mercaptopyrimidine system using [3+3] heterocyclization process has been less explored there are some published examples in literature. Thus, Miyamoto's 24 group had investigated the interaction of 2-(ethoxymethylidene)malononitrile (2) with methyl N'-cycloalkylylidenecarbamohydrazonothioates 1, which led to the formation of spirocondensed heterocyclic systems 3 containing pyrimidine ring (Scheme 1).The known methods for synthesis of thioxopyrimidines and their condensed analogs with exocyclic sulfur atom are summarized and discussed. The most popular approaches are based on [3+3], [4+2], [5+1] cyclization processes or domino reactions. The literature data analysis shows that the title compounds possess diverse biological activities, such as antioxidant, radioprotective, analgesic, antiinflammatory, antihypertensive, anxiolytic, anamnestic, anticonvulsant, antimicrobial, fungicidal, herbicidal, antiviral, and anticancer.

show abstract

“…Recently, the potent in vitro antifungal activity of tacrolimus (FK 506 Fujimycin; Figure 1 ) toward fungi and oomycetes was demonstrated [ 28 ]. Tacrolimus is a macrolide lactone isolated and characterized from Streptomyces tsukubaensis [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

“…Some components of the calcium-calcineurin signaling pathway vital for fungal growth have been identified as potential and effective targets for the development of new therapeutic drugs [ 31 , 32 ]. Tacrolimus has not been analyzed in the context of plant protection in agriculture thus far, beyond our own study [ 28 ], and it is not found in the “Pesticide Properties DataBase” [ 33 ].…”

Section: Introductionmentioning

confidence: 99%

Combined Application of Tacrolimus with Cyproconazole, Hymexazol and Novel {2-(3-R-1H-1,2,4-triazol-5-yl)phenyl}amines as Antifungals: In Vitro Growth Inhibition and In Silico Molecular Docking Analysis to Fungal Chitin Deacetylase

Antypenko

Meyer

Sadyk

et al. 2023

JoF

Self Cite

View full text Add to dashboard Cite

Agents with antifungal activity play a vital role as therapeutics in health care, as do fungicides in agriculture. Effectiveness, toxicological profile, and eco-friendliness are among the properties used to select suitable substances. Furthermore, a steady supply of new agents with different modes of action is required to counter the well-known potential of human and phyto-pathogenic fungi to develop resistance against established antifungals. Here, we use an in vitro growth assay to investigate the activity of the calcineurin inhibitor tacrolimus in combination with the commercial fungicides cyproconazole and hymexazol, as well as with two earlier reported novel {2-(3-R-1H-1,2,4-triazol-5-yl)phenyl}amines, against the fungi Aspergillus niger, Colletotrichum higginsianum, Fusarium oxysporum and the oomycete Phytophthora infestans, which are notoriously harmful in agriculture. When tacrolimus was added in a concentration range from 0.25 to 25 mg/L to the tested antifungals (at a fixed concentration of 25 or 50 mg/L), the inhibitory activities were distinctly enhanced. Molecular docking calculations revealed triazole derivative 5, (2-(3-adamantan-1-yl)-1H-1,2,4-triazol-5-yl)-4-chloroaniline), as a potent inhibitor of chitin deacetylases (CDA) of Aspergillus nidulans and A. niger (AnCDA and AngCDA, respectively), which was stronger than the previously reported polyoxorin D, J075-4187, and chitotriose. The results are discussed in the context of potential synergism and molecular mode of action.

show abstract

Tacrolimus as Antifungal Agent

Cited by 7 publications

References 30 publications

Identifying Potential Molecular Targets in Fungi Based on (Dis)Similarities in Binding Site Architecture with Proteins of the Human Pharmacolome

Identifying Potential Molecular Targets in Fungi Based on (Dis)Similarities in Binding Site Architecture with Proteins of the Human Pharmacolome

Preparation and biological properties of 2-thio-containing pyrimidines and their condensed analogs

Combined Application of Tacrolimus with Cyproconazole, Hymexazol and Novel {2-(3-R-1H-1,2,4-triazol-5-yl)phenyl}amines as Antifungals: In Vitro Growth Inhibition and In Silico Molecular Docking Analysis to Fungal Chitin Deacetylase

Contact Info

Product

Resources

About