Chan-Hong Ahn

Sargachromanols as inhibitors of Na+/K+ ATPase and isocitrate lyase.

Sargachromanols A-P (1-16), 16 meroterpenoids of the chromene class isolated from the brown alga Sargassum siliquastrum, were evaluated for their inhibitory activities toward Na(+)/K(+) ATPase from porcine cerebral cortex and isocitrate lyase (ICL) from Candida albicans. These studies led to the identification of compounds 4, 6, 8, and 12 as potent Na(+)/K(+) ATPase inhibitors. Compounds 12, 13, and 16 exhibited moderate ICL inhibitory activity. Compound 12 also showed weak antibacterial activity. The preliminary structure-activity relationship of these compounds is described to elucidate the essential structural requirements.

New Benzoxazine Secondary Metabolites from an Arctic Actinomycete

Two new secondary metabolites, arcticoside (1) and C-1027 chromophore-V (2), were isolated along with C-1027 chromophore-III and fijiolides A and B (3–5) from a culture of an Arctic marine actinomycete Streptomyces strain. The chemical structures of 1 and 2 were elucidated through NMR, mass, UV, and IR spectroscopy. The hexose moieties in 1 were determined to be d-glucose from a combination of acid hydrolysis, derivatization, and gas chromatographic analyses. Arcticoside (1) and C-1027 chromophore-V (2), which have a benzoxazine ring, inhibited Candida albicans isocitrate lyase. Chromophore-V (2) exhibited significant cytotoxicity against breast carcinoma MDA-MB231 cells and colorectal carcinoma cells (line HCT-116), with IC50 values of 0.9 and 2.7 μM, respectively.

Candida albicans PHO81 is required for the inhibition of hyphal development by farnesoic acid.

Farnesoic acid is a signaling molecule that inhibits the transition from budding yeast to filament formation in Candida albicans, but the molecular mechanism regulated by this substance is unknown. In this study, we analyzed the function of CaPHO81, which is induced by farnesoic acid. The pho81Δ mutant cells existed exclusively as filaments under favorable yeast growth conditions. Furthermore, the inhibition of hyphal growth and repression of CPH1, EFG1, HWP1, and GAP1 mRNA expression in response to farnesoic acid were defective in pho81Δ mutant cells. These data suggest a role for CaPHO81 in the inhibition of hyphal development by farnesoic acid.

Additional Sesterterpenes and a Nortriterpene Saponin from the Sponge Clathria gombawuiensis

Three new terpene metabolites (1-3) were isolated from the marine sponge Clathria gombawuiensis collected from Korean waters. On the basis of the results of combined spectroscopic analyses, the structures of phorone B (1) and ansellone C (2) were determined to be the sesterterpenes of the phorone and ansellone classes, respectively, whereas the saponin gombaside A (3) was a nortriterpene sodium O-sulfonato-glucuronide of the rare 4,4,14-trimethylpregnane class. The absolute configuration of the glucuronate of 3 was assigned by an application of the phenylglycine methyl ester (PGME) method. The new compounds exhibited moderate cytotoxicity against A549 and K562 cell lines, and compound 3 showed antibacterial activity. The cytotoxicity of 1 may be related to the presence of a free phenolic -OH group, as the corresponding O-methoxy derivative 4 is inactive.

Inhibition of Candida albicans isocitrate lyase activity by cadiolides and synoilides from the ascidian Synoicum sp.

Tris-aromatic furanones (1-4) and related bis-aromatic diesters (5 and 6) isolated from the dark red ascidian Synoicum sp., were evaluated for their inhibitory activities toward Candida albicans isocitrate lyase (ICL). These studies led to the identification of compounds 1, 3, and 4 as potent ICL inhibitors, with IC50 values of 7.62, 17.16, and 10.36 μM, respectively. Growth phenotype of ICL deletion mutants and Northern blot analysis data indicated that compound 1 inhibits the ICL expression in C. albicans under C2 carbon utilizing condition.

Inhibition of yeast-to-hypha transition in Candida albicans by phorbasin H isolated from Phorbas sp.

Phorbasin H is a diterpene acid of a bisabolane-related skeletal class isolated from the marine sponge Phorbas sp. In this study, we examined whether phorbasin H acted as a yeast-to-hypha transition inhibitor of Candida albicans. Growth experiments suggest that this compound does not inhibit yeast cell growth but inhibits filamentous growth in C. albicans. Northern blot analysis of signaling pathway components indicated that phorbasin H inhibited the expression of mRNAs related to cAMP–Efg1 pathway. The exogenous addition of db-cAMP to C. albicans cells had no influence on the frequency of hyphal formation. The expression of hypha-specific HWP1 and ALS3 mRNAs, both of which are positively regulated by the important regulator of cell wall dynamics Efg1, was significantly inhibited by the addition of phorbasin H. This compound also reduced the ability of C. albicans cells to adhere in a dose-dependent manner. Our findings suggest that phorbasin H impacts the activity of the cAMP–Efg1 pathway, thus leading to an alteration of C. albicans morphology.

A farnesoic acid‐responsive transcription factor, Hot1, regulates yeast‐hypha morphogenesis in Candida albicans

Candida albicans hyphal formation is inhibited by a quorum‐sensing molecule, farnesoic acid, which accumulates in the medium as the cells proliferate. We recently showed that Pho81 is essential for the inhibition of hyphal growth by farnesoic acid. Here, we describe a newly identified regulator, Hot1, which increases the expression of PHO81. The binding site of Hot1 in the PHO81 promoter region was identified by DNase I protection assay. The hot1Δ mutant grows extensively as filaments. Furthermore, the inhibition of hyphal formation and the repression of major signaling pathway components in response to farnesoic acid are defective in hot1Δ mutant cells. These data suggest an important role for HOT1 in the inhibition of hyphal development by farnesoic acid in this fungus.