Discovery of uracil-based histone deacetylase inhibitors able to reduce acquired antifungal resistance and trailing growth in Candida albicans

Mai, Antonello; Rotili, Dante; Massa, S.; Brosch, Gerald; Simonetti, Giovanna; Passariello, Claudio; Palamara, Anna Teresa

doi:10.1016/j.bmcl.2006.12.028

Cited by 85 publications

(54 citation statements)

References 52 publications

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“…116 In combination with fluconazole, treatment with several investigational uracil-based hydroxamates inhibited induction of resistance to fluconazole in Candida spp. 117 TSA and SAHA also caused a 90% reduction in C. albicans adherence to human cultured pneumocytes. 118 Increasing experience in using HDACis to treat cancer will aid testing of the efficacy of combinations of HDACis and azoles Effects on Candida.…”

Section: Hdacismentioning

confidence: 89%

Direct effects of non-antifungal agents used in cancer chemotherapy and organ transplantation on the development and virulence ofCandidaandAspergillusspecies

2011

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Section: Hdacismentioning

confidence: 89%

Direct effects of non-antifungal agents used in cancer chemotherapy and organ transplantation on the development and virulence ofCandidaandAspergillusspecies

2011

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“…Finally, (1,3)-␤-D-glucan levels in the fungal cell wall contribute to biofilm azole resistance (414). Biofilms are known to have increased (1,3)-␤-D-glucan content, and the addition of glucanases increases the efficacy of fluconazole against in vitro and in vivo biofilms (355). With the clinical challenges of effectively treating C. albicans biofilms, it is critical to identify additional mechanisms that contribute to the azole resistance of these cellular communities.…”

Section: Biofilmsmentioning

confidence: 99%

Regulatory Circuitry Governing Fungal Development, Drug Resistance, and Disease

Shapiro

Robbins

Cowen

2011

Microbiol Mol Biol Rev

492

547

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SUMMARY Pathogenic fungi have become a leading cause of human mortality due to the increasing frequency of fungal infections in immunocompromised populations and the limited armamentarium of clinically useful antifungal drugs. Candida albicans , Cryptococcus neoformans , and Aspergillus fumigatus are the leading causes of opportunistic fungal infections. In these diverse pathogenic fungi, complex signal transduction cascades are critical for sensing environmental changes and mediating appropriate cellular responses. For C. albicans , several environmental cues regulate a morphogenetic switch from yeast to filamentous growth, a reversible transition important for virulence. Many of the signaling cascades regulating morphogenesis are also required for cells to adapt and survive the cellular stresses imposed by antifungal drugs. Many of these signaling networks are conserved in C. neoformans and A. fumigatus , which undergo distinct morphogenetic programs during specific phases of their life cycles. Furthermore, the key mechanisms of fungal drug resistance, including alterations of the drug target, overexpression of drug efflux transporters, and alteration of cellular stress responses, are conserved between these species. This review focuses on the circuitry regulating fungal morphogenesis and drug resistance and the impact of these pathways on virulence. Although the three human-pathogenic fungi highlighted in this review are those most frequently encountered in the clinic, they represent a minute fraction of fungal diversity. Exploration of the conservation and divergence of core signal transduction pathways across C. albicans , C. neoformans , and A. fumigatus provides a foundation for the study of a broader diversity of pathogenic fungi and a platform for the development of new therapeutic strategies for fungal disease.

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“…Several pyrimidine-based derivatives have been developed as anticancer agents [1e4], and antiviral agents against HIV [5e9], HBV [10,11], HCV [12], and HSV [13,14]. In addition, several pyrimidine derivatives have long been recognized as potent bactericidal [15e19], fungicidal [20,21] and antiprotozoal agents [22e25]. 1-[(2-Hydroxyethoxy)methyl]-6-(phenylthio) thymine (HEPT) and its related derivatives [26e30] were discovered as potent and selectively active agents against HIVÀ1 infections.…”

Section: Introductionmentioning

confidence: 99%

Spectroscopic and electronic structure calculation of a potential chemotherapeutic agent 5-propyl-6-(p-tolylsulfanyl)pyrimidine-2,4(1H,3H)-dione using first principles

Al-Alshaikh

Al‐Deeb

Alzoman

et al. 2015

Journal of Molecular Structure

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Discovery of uracil-based histone deacetylase inhibitors able to reduce acquired antifungal resistance and trailing growth in Candida albicans

Cited by 85 publications

References 52 publications

Direct effects of non-antifungal agents used in cancer chemotherapy and organ transplantation on the development and virulence ofCandidaandAspergillusspecies

Direct effects of non-antifungal agents used in cancer chemotherapy and organ transplantation on the development and virulence ofCandidaandAspergillusspecies

Regulatory Circuitry Governing Fungal Development, Drug Resistance, and Disease

Spectroscopic and electronic structure calculation of a potential chemotherapeutic agent 5-propyl-6-(p-tolylsulfanyl)pyrimidine-2,4(1H,3H)-dione using first principles

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