Novel small molecules for the treatment of infections caused by<i>Candida albicans</i>: a patent review (2002 – 2010)

Calugi, Chiara; Trabocchi, Andrea; Guarna, Antonio

doi:10.1517/13543776.2011.551116

Cited by 25 publications

(28 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Traditional antifungal therapies are effective but toxic to patients, and so there has been considerable interest in developing novel treatments that exploit fungal-specific biology such as synthesis of the primary septum. A variety of natural and synthetic chitin synthase inhibitors have been described recently, including several compounds with potency in vitro against orthologues of ScChs2, and the clinical potential of such compounds is currently under investigation (Calugi et al, 2011). Our data suggest that Cyk3 and the interaction of the Inn1 C2-domain with Chs2 represent alternative targets for the development of novel small molecule inhibitors of cytokinesis in pathogenic yeasts.…”

Section: Discussionmentioning

confidence: 80%

Inn1 and Cyk3 regulate chitin synthase during cytokinesis in budding yeasts

Devrekanli

Foltman

Roncero

et al. 2012

Journal of Cell Science

View full text Add to dashboard Cite

SummaryThe chitin synthase that makes the primary septum during cell division in budding yeasts is an important therapeutic target with an unknown activation mechanism. We previously found that the C2-domain of the Saccharomyces cerevisiae Inn1 protein plays an essential but uncharacterised role at the cleavage site during cytokinesis. By combining a novel degron allele of INN1 with a point mutation in the C2-domain, we screened for mutations in other genes that suppress the resulting defect in cell division. In this way, we identified 22 dominant mutations of CHS2 (chitin synthase II) that map to two neighbouring sites in the catalytic domain. Chs2 in isolated cell membranes is normally nearly inactive (unless protease treatment is used to bypass inhibition); however, the dominant suppressor allele Chs2-V377I has enhanced activity in vitro. We show that Inn1 associates with Chs2 in yeast cell extracts. It also interacts in a yeast two-hybrid assay with the N-terminal 65% of Chs2, which contains the catalytic domain. In addition to compensating for mutations in the Inn1 C2-domain, the dominant CHS2 alleles suppress cytokinesis defects produced by the lack of the Cyk3 protein.Our data support a model in which the C2-domain of Inn1 acts in conjunction with Cyk3 to regulate the catalytic domain of Chs2 during cytokinesis. These findings suggest novel approaches for developing future drugs against important fungal pathogens.

show abstract

Section: Discussionmentioning

confidence: 80%

Inn1 and Cyk3 regulate chitin synthase during cytokinesis in budding yeasts

Devrekanli

Foltman

Roncero

et al. 2012

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…Beside the screening for compounds with fungicidal or fungistatic activity and the description of novel potential antimycotic therapeutics (reviewed by Calugi et al (2011)), the recent years also saw the development of novel approaches to the search for antifungal agents (for example BurgerKentischer et al, 2011;Lafleur et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Identification of inhibitors of yeast-to-hyphae transition in Candida albicans by a reporter screening assay

Heintz‐Buschart¹,

Eickhoff²,

Hohn³

et al. 2013

Journal of Biotechnology

View full text Add to dashboard Cite

Candida albicans is one of the most common opportunistic fungal pathogens, causing lifethreatening disease in immunocompromised patients. As it is not primarily a pathogen, but can exist in a commensal state, we aimed at the identification of new anti-infective compounds which do not eradicate the fungus, but primarily disable a virulence determinant. The yeast-hyphae-dimorphism of C. albicans is considered a major contributor to fungal disease, as mutants locked into either yeast or hyphal state have been shown to be less virulent in the mouse-model.We devised a high-throughput screening procedure which allows us to find inhibitors of the induction of hyphae. Hyphae-formation was induced by nitrogen starvation at 37 °C and neutral pH in a reporter strain, which couples promotor activity of the hyphae-specific HWP1 to β-

show abstract

“…Unfortunately, the overuse of broad-spectrum antibiotics has resulted in the emergence of many resistant infectious pathogens, such as fluconazoleresistant C. albicans strains (Brion et al 2007;Gamacho-Montero et al 2010;Martínez et al 2002). Therefore, the search for a new class of therapeutic agents is critical and pressing (Calugi et al 2011). Natural products, medicinal plants, and their derivatives have been used as new sources of alternative therapies to treat or relieve diseases (Gurib-Fakin 2006).…”

Section: Discussionmentioning

confidence: 99%