Bendaha H~Bellaoui M, 2011

Pubmed ID 21723647
Title New azole antifungal agents with novel modes of action: synthesis and biological studies of new tridentate ligands based on pyrazole and triazole.
Authors Hasnae Bendaha, Lisa Yu, Rachid Touzani, Rachid Souane, Guri Giaever, Corey Nislow, Charles Boone, Sghir El Kadiri, Grant W Brown, Mohammed Bellaoui
Abstract The synthesis and extensive biological study of two new tridentates ligands based on pyrazole and triazole are described. The antifungal activity against the budding yeast cells of the newly synthesized compounds was determined. These compounds were toxic to yeast cells. Cell cycle analysis suggested that treatment with these compounds impairs cell division in G1 of the cell cycle. Using yeast-based functional genomics technologies, we found that these compounds tolerance requires DNA repair pathway and SKI complex function. We have also found that the PKC1 heterozygous deletion strain was the most sensitive to these compounds using HaploInsufficiency Profiling, suggesting that the Pkc1 protein may be the target for these compounds. These results strongly suggest that these compounds induce DNA damage and thus exert a different mechanism of action compared to other azole derivatives. These two compounds might therefore represent promising lead compounds for further development of antifungal drugs for human therapy.
Citation Eur J Med Chem 2011; 46:4117-24

Datasets

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Paper Phenotype Condition Medium Collection Tested mutants Data Details
Bendaha H~Bellaoui M, 2011 growth (pooled culture, microarray) compound 3 hap ? ~5,000 Discrete
Bendaha H~Bellaoui M, 2011 growth (pooled culture, microarray) compound 6 hom N/A Discrete
Bendaha H~Bellaoui M, 2011 growth (pooled culture, microarray) compound 6 het N/A Discrete
Bendaha H~Bellaoui M, 2011 growth (pooled culture, microarray) compound 3 het N/A None

Curation history

Tested strains

Oct. 30, 2020 Request sent.
Oct. 30, 2020 To request.

Data

Oct. 30, 2020 Request sent.
Oct. 30, 2020 To request.