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Lipids of Candida Albicans
Published in Rajendra Prasad, Mahmoud A. Ghannoum, Lipids of Pathogenic Fungi, 2017
R. Prasad, A. Koul, P. K. Mukherjee, M. A. Ghannoum
It seems that the biosynthetic pathways of sterols share a commonality, except the biosynthesis of episterol in both S. cerevisiae and C. albicans22,60 Episterol is converted to ergosterol through different pathways in S. cerevisiae and C. albicans. In C. albicans, the intermediates formed between episterol and ergosterol are ergosta-7-en-3-ol and ergosta-5,7-diene-3-β-ol, whereas in S. cerevisiae ergosta-7,22,24(28)-triene-3-α-ol and ergosta-5,7,22,24(28)-tetra-ene-3-β-ol are formed.23
Biological exploration of a novel 1,2,4-triazole-indole hybrid molecule as antifungal agent
Published in Journal of Enzyme Inhibition and Medicinal Chemistry, 2020
Fabrice Pagniez, Nicolas Lebouvier, Young Min Na, Isabelle Ourliac-Garnier, Carine Picot, Marc Le Borgne, Patrice Le Pape
Several events are involved in the membrane biosynthesis, especially the production of lipids as sterols and phospholipids. We demonstrated that 8 g inhibits Candida ergosterol synthesis as observed with other azole drugs. This inhibition led to membrane integrity perturbations through ergosterol depletion, precursor accumulation (lanosterol) and production of alternative 14α-methyl sterols (14α-methyl-fecosterol, 14α-methyl-episterol and 14α-methyl-3,6-diol). Identification of 14α-methylated sterols evidenced a blockage of CYP51 as a way of action of 8 g. Interestingly, the effects of 8 g on sterol metabolism are observed in CAAL93 (fluconazole susceptible strain) at 4 ng/mL whereas the same results are observed after fluconazole treatment at a 1000-fold higher concentration (4 µg/mL). Moreover, the same effects are seen when fluconazole-resistant strains (CAKR7 and CAGL2) were treated by 8 g at 4 µg/mL whereas nothing happened after treatment with the same dose of fluconazole. These results show the potency of this new indole-triazole derivative compound.