Antifungal activity of liriodenine on agents of systemic mycoses, with emphasis on the genus Paracoccidioides

Endemic systemic mycoses remain a health challenge, since these opportunistic diseases are increasingly infecting immunosuppressed patients. The simultaneous use of antifungal compounds and other drugs to treat infectious or non-infectious diseases has led to several interactions and undesirable effects. Thus, new antifungal compounds should be investigated. The present study aimed to evaluate the activity of liriodenine extracted from Annona macroprophyllata on agents of systemic mycoses, with emphasis on the genus Paracoccidioides. Methods: The minimum inhibitory concentration (MIC) and minimum fungicide concentration (MFC) were determined by the microdilution method. The cellular alterations caused by liriodenine on a standard P. brasiliensis (Pb18) strain were evaluated by transmission and scanning electron microscopy. Results: Liriodenine was effective only in 3 of the 8 strains of the genus Paracoccidioides and in the Histoplasma capsulatum strain, in a very low concentration (MIC of 1.95 µg.mL-1); on yeasts of Candida spp. (MIC of 125 to 250 µg.mL-1), including C. krusei (250 µg.mL-1), which has intrinsic resistance to fluconazole; and in Cryptococcus neoformans and Cryptococcus gattii (MIC of 62.5 µg.mL-1). However, liriodenine was not effective against Aspergillus fumigatus at the studied concentrations. Liriodenine exhibited fungicidal activity against all standard strains and clinical isolates that showed to be susceptible by in vitro tests. Electron microscopy revealed cytoplasmic alterations and damage to the cell wall of P. brasiliensis (Pb18). Conclusion: Our results indicate that liriodenine is a promising fungicidal compound that should undergo further investigation with some chemical modifications.(AU)

Antibacterial constituents from roots of Zanthoxylum nitidum / 中草药

Objective: To isolate and identify the antibacterial constituents from the roots of Zanthoxylum nitidum. Methods: Bioassay-guided fractionation led to the isolation of compounds from the roots of Z. nitidum by using various chromatographic techniques such as silica gel, alumina, preparative TLC, and HPLC, and their chemical structures were then elucidated on the basis of spectroscopic data, including NMR, MS analysis, and their physicochemical properties. Results: Eleven compounds were isolated from the bioactive extracts in the roots of Z. nitidum and then were identified as skimmianine (1), oxychelerythrine (2), 8-methoxy-dihydrochelerythrine (3), β-sitosterol (4), L-sesamin (5), 8-methoxy-9-demethoxyldihydrochelerythrine (6), 4-hydroxy-N- methylproline (7), liriodenine (8), avicine (9), nitidine (10), and isobutyl benzoate (11), respectively. Compounds 1, 3, 6, 8, and 10 showed the potential inhibition on Staphylococcus aureus. Compound 8 showed the most potential inhibitory activity with MIC value of 31.3 μg/mL; Further studies demonstrated that compound 8 inhibited the clinical multidrug-resistant methicillin-resistant Staphylococcus aureus (MRSA) activity with MIC value of 93.8 μg/mL, significantly. Conclusion: A series of bioactive alkaloids with the anti-staphylococcal activities were identified from the roots of Z. nitidum. Compounds 7, 9, and 11 are obtained from this plant for the first time, and the potential anti-staphylococcal activity of compound 8 against MRSA has been demonstrated, which has provided the chemical template as a new anti-bacterial agent against clinical multidrug-resistant MRSA infection.

Studies on bioactive constituents in bark of Tsoongiodendron odorum / 中草药

Object To study the chemical constituent and the bioactivity in the bark of Tsoongiodendron odorum Chun Methods By bioactive following method, the extracts of both EtOAc and n BuOH in the bark of T odorum were screened for in vitro anti tumor activity Results Five constituents were obtained Among them, three from EtOAc fraction belonged to germacranolides They were costunolide (Ⅰ), parthenolide (Ⅱ) and dihydroparthenolide (Ⅲ) The other two were from the fraction of n BuOH, one was an oxoaporphinoid alkaloid, liriodenine (Ⅳ), and the last was a furanone, 2, 3 dihydroxyl 2 methyl butylrolactone (Ⅴ) Conclusion All the above five compounds are found for the first time from this plant Compounds Ⅰ, Ⅱ, Ⅳ, and Ⅴ show the cytotoxic activities against a variety of tumor cell strains, respectively