Antifungal and Cytotoxic Activity of Withanolides from Acnistus arborescens

Abstract

Three compounds were isolated from Acnistus arborescens, a tree commonly used in South and Central America in traditional medicine against several infectious diseases, some of which are caused by fungi. Bioassay-guided fractionation of a MeOH extract of leaves, based on its anti-Pneumocystis carinii activity, led to the isolation of compounds 1-3. Mono- and bidimensional NMR analyses enabled identification of two new withanolides, (20R,22R)-5beta,6beta-epoxy-4beta,12beta,20-trihydroxy-1-oxowith-2-en-24-enolide (1) and (20R,22R)-16beta-acetoxy-3beta,4beta;5beta,6beta-diepoxy-12beta,20-dihydroxy-1-oxowith-24-enolide (2), and withanolide D (3). Antifungal activity on 13 fungi responsible for human infections (five dermatophytes, one nondermatophyte mold, six yeasts, and Pneumocystis carinii) was examined. Cytotoxicity of these compounds was also evaluated in vitro.

Phytochemical Study of the Genus Salpichroa (Solanaceae), Chemotaxonomic Considerations, and Biological Evaluation in Prostate and Breast Cancer Cells

“…Comparison of salpichrolide A and salpichrolide C showed that the cleavage of the 5,6‐epoxy group to give the 5 α ,6 β ‐diol abolished the cytotoxic activity, in agreement with results previously reported in the literature . The presence of a hydroxy group at C(12) position ( α or β ) led to a loss of activity (LNCaP and T47D), this is observed when comparing the compounds salpichrolide A and salpichrolide T and compound 6 , in agreement with results previously reported for compounds with similar structural features . Finally, no loss of activity was observed when the 5 α ,6 α ‐epoxy functionality was replaced by 5 α ‐chloro‐6 β ‐hydroxy system (salpichrolide A and 1 ).…”

Antiproliferative withanolides from the solanaceae: A structure-activity study

“…12-OH group: 12β-Hydroxywithanolide D 49 is slightly less potent than withanolide D 48 [22]. 14,15-epoxy-group: 14α,15α-Epoxywithaferin A 50 is less potent than withaferin A 1 [35].…”

“…From the biogenetic origin, it is likely that type I compounds are precursors to the more advanced structural types II−XXII. Type I withanolides that display the most promising antiproliferative characteristics also contain Δ 2 -1-oxo-functionality in ring A, a 5β,6β-epoxy-group in ring B, and a nine-carbon side chain incorporating the δ-lactone functionality found in withaferin A 1 [17], withacnistin 59 [18,19], withanolide D 48 [20][21][22][23], withanolide E 36 [8,[24][25][26][27], and 4β-hydroxywithanolide E 37 (Fig. 4) [8,[24][25][26][27].…”

Antifungal Activity of 10 Guadeloupean Plants

“…Nonetheless, we did observe an anti‐ Pneumocystis activity for C. odorata (MIC 100 ≤ 1 µg/ml for the hydro‐ethanolic extract) and A. arborescens (MIC 100 = 100 µg/ml for hexanic extract and 10 µg/ml for ethanolic or hydro‐ethanolic extracts due to withanolides) (Roumy et al ., ).…”