Styrylpyrone, isolated from an Amazon plant, induces cell cycle arrest and autophagy in Leishmania amazonensis

Abstract

The search for bioactive compounds against diseases is imperative and the richness of the Amazon provides a large source to be explored. Current therapies for the treatment of parasitic infections have severe side effects and low efficacy, which makes the development of an effective chemotherapy extremely important. In this study, we describe the isolation of styrylpyrone 4-methoxy-6-(11,12-methylenedioxytrans-styryl)-2-pyrone (SP), from the Amazonian tree species, Aniba panurensis, the in vitro activity against Leishmania amazonensis promastigotes, and its in silico pharmacokinetics properties. The results showed morphological and ultrastructural alterations, cell cycle impairment, increased reactive oxygen species production, accumulation of lipid bodies and formation of autophagic vacuoles in SP-treated parasites. In silico studies revealed that the compound has a high drug-score, which is encouraging for further investigation. Our results indicate that SP is a promising drug candidate, which induces alterations in L. amazonensis leading to parasite death through cell cycle arrest and autophagy.

Research on the Interaction Mechanism and Structural Changes in Human Serum Albumin with Hispidin Using Spectroscopy and Molecular Docking

“…All examined interactions exhibit n values very close to 1, indi can bind exclusively to a single binding site in HSA. The Ka is approx L/mol, suggesting that hispidin and HSA have a significant interactio sults presented in Table 3 reveal that the Ka values for the hispidin-HS K decreased to 2.84 × 10 4 and 3.09 × 10 4 L/mol when SDS or urea w indicates that SDS or urea has the potential to disrupt the hispidin-HS 1) to (10). The structure of hispidin is matched by the inset.…”

“…tration was 0-45 µmol/L (1)→ (10). Curve 11 is the UV spectrum of only hispidin with a concentration of 45 µmol/L.…”

“…As a secondary metabolite, hispidin is found in numerous fungus families, including Hymenochaetaceae [3], Hymenogastraceae [4], Phaeolaceae [5], Omphalotaceae [6], and Cortinariaceae [7]. Additionally, several plants, such as Equisetum arvense [8], Pistacia atlantica [9], Leishmania amazonensis [10], and Goniothalamus umbrosus [11], also contain hispidin and its derivatives [12]. Hispidin is attracting the attention of researchers for its potential in preventing and treating cancer [13], cardiovascular disease [14], neurodegenerative illnesses [15], and viral infections [16].…”

Could natural terpenes be an alternative for the treatment of neglected tropical diseases?

“…Another ultrastructural modification observed in L. mexicana promastigotes following treatment with enhydrin ( 9 ), uvedalin ( 10 ), and polymatin B ( 11 ), was the formation of multilamellar structures suggesting the presence of autophagic vacuoles (Figure 5) (Ulloa et al., 2017). Abnormal activation of the autophagic pathway in Leishmania spp, as stimulated by numerous compounds or bioactive substances, is correlated with parasite cell death (Bera et al., 2003; Fernandes et al., 2021; Petersen et al., 2021).…”

Transcriptome Analysis Reveals the Putative Polyketide Synthase Gene Involved in Hispidin Biosynthesis in Sanghuangporus sanghuang

“…Hispidin and hispidin derivatives are also found in other fungal families such as the families Phaeolaceae [ 16 ], Omphalotaceae ( Neonothopanus nambi ) [ 17 ], Strophariaceae ( Hypholoma sublateritium ), and Cortinariaceae ( Cortinarius glaucopus ) [ 11 ]. Furthermore, hispidin derivatives were also identified in some plants, including Equisetum arvense [ 18 ], Pistacia atlantica [ 19 ], Leishmania amazonensis [ 20 ], and Goniothalamus umbrosus [ 21 ].…”