Fungistatic Effect of Phthalide Lactones on Rhodotorula mucilaginosa.

Currently, there is an increasing number of cases of fungal infections caused by opportunistic strains of the yeast Rhodotorula mucilaginosa, mainly in immunocompromised patients during hospitalization. The excessive use of antibiotics and azole compounds increases the risk of resistance to microorganisms. A new alternative to these drugs may be synthetic phthalide lactones with a structure identical to or similar to the natural ones found in celery plants, which show low toxicity and relatively high fungistatic activity. In the present study, the fungistatic activity of seven phthalide lactones was determined against R. mucilaginosa IHEM 18459. We showed that 3-n-butylidenephthalide, the most potent compound selected in the microdilution test, caused a dose-dependent decrease in dry yeast biomass. Phthalide accumulated in yeast cells and contributed to an increase in reactive oxygen species content. The synergistic effect of fluconazole resulted in a reduction in the azole concentration required for yeast inhibition. We observed changes in the color of the yeast cultures; thus, we conducted experiments to prove that the carotenoid profile was altered. The addition of lactones also triggered a decline in fatty acid methyl esters.

Antimicrobial activity of extracts and phthalides occurring in Apiaceae plants.

Apiaceae plants exhibit a broad spectrum of activities, for instance, antithrombotic, hypotensive, antioxidant, and insecticidal. They also provide a source of phthalides, which display antimicrobial activity. Considering the fact of rising resistance of both bacteria and fungi against commonly used antibiotics, developing of new naturally derived compounds is undeniably attractive approach. To our best knowledge, there are no other reviews concerning this subject in the literature. In view of above, an attempt to summarize an antimicrobial potential of isolated compounds and extracts from Apiaceae plants has been made, by specifying techniques of activity determination and methods of extraction. Techniques of antimicrobial activity evaluation are mainly based on bioautography, diffusion, and dilution methods. Therefore, we focused on in vitro data described in literature so far.

Synthesis and fungistatic activity of bicyclic lactones and lactams against Botrytis cinerea, Penicillium citrinum, and Aspergillus glaucus.

Six analogues of natural trans-4-butyl-cis-3-oxabicyclo[4.3.0]nonan-2-one (3) and three derivatives, 11, 12, and 13, of Vince lactam (10) were synthesized and tested as fungistatic agents against Botrytis cinerea AM235, Penicillium citrinum AM354, and six strains of Aspergillus. Moreover, bioresolution carried out by means of whole cell microorganisms and commercially available enzymes afforded opposite enantiomerically enriched (-) and (+) isomers of Vince lactam (10), respectively. The effect of compound structures and stereogenic centers on biological activity has been discussed. The highest fungistatic activity was observed for four lactones: 3, 4, 7, and 8 (IC50 = 104.6-115.2 µg/mL) toward B. cinerea AM235. cis-5,6-Epoxy-2-aza[2.2.1]heptan-3-one (13) indicated significant fungistatic activity (IC50 = 107.1 µg/mL) against Aspergillus glaucus AM211. trans-4-Butyl-cis-3-oxabicyclo[4.3.0]nonan-2-one (3) and trans-4-butyl-cis-3-oxabicyclo[4.3.0]non-7-en-2-one (7) exhibited high fungistatic activity (IC50 = 143.2 and 110.2 µg/mL, respectively) against P. citrinum AM354 as well.