Annona cornifolia A. St. -Hil. is a small annual perennial tree found in the Brazilian savannah; their green fruit is popularly used in the treatment of ulcers. The acetogenins isolated from the seeds of Annona cornifolia previously showed to possess antioxidant activity. In continuation of our investigations on the biological activities of acetogenins, four binary mixtures and ten pure adjacent bis-tetrahydrofuran annonaceous acetogenins were evaluated: the cytotoxic (against three human tumor cell lines), antifungal (against Paracoccidioides brasiliensis), trypanocidal (against Trypanosoma cruzi) and leishmanicidal (against Leishmania amazonensis) activities. Acetogenins presented cytotoxic activity confirming their potential use in anti-cancer therapy. Regarding leishmanicidal and trypanocidal activities, an inhibition of 87% of L. amazonensis amastigotes and 100% of T. cruzi amastigotes and trypomastigotes was observed, when tested at the concentration of 20 µg mL-1. Moreover, six acetogenins showed more activity against all the three tested isolates of P. brasiliensis than trimethoprim-sulfamethoxazole, a drug used for treating paracoccidioidomycosis. Thus, acetogenins may be an alternative in treating a number of diseases that have a huge impact on millions of people worldwide. This paper reports for the first time the antifungal, leishmanicidal and trypanocidal activities for these acetogenins.
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Phytochemistry
December 2024
Centre for Natural and Human Sciences, Federal University of ABC, Santo Andre, SP, 09280-560, Brazil. Electronic address:
As part of our continuous study on the Annonaceae species Porcelia macrocarpa, in the present work, eight chemically related 2-alkyl-3-hydroxy-4-methyl-γ-lactones (1-8) were isolated. Their structures were characterised by NMR, MS, and VCD. Their antitrypanosomal activity was evaluated in vitro against intracellular amastigotes with EC values ranged from 13.
View Article and Find Full Text PDFPest Manag Sci
November 2024
Department of Soil and Environmental Sciences, University of Wisconsin-Madison, Madison, WI, USA.
Plant-parasitic nematodes are among the most destructive plant pathogens, resulting in a global annual economic loss of about 358 billion dollars. Using synthetic nematicides to control plant-parasitic nematodes has resulted in broad-spectrum toxicity to the environment. Plant-derived secondary metabolites have recently emerged as viable options that provide effective, greener, and renewable routes for managing plant-parasitic nematodes in various cropping systems.
View Article and Find Full Text PDFInt J Mol Sci
October 2024
Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga 849-8501, Japan.
Patients with chronic myeloid leukemia (CML) respond to tyrosine kinase inhibitors (TKIs); however, CML leukemic stem cells (LSCs) exhibit BCR::ABL kinase-independent growth and are insensitive to TKIs, leading to disease relapse. To prevent this, new therapies targeting CML-LSCs are needed. Rates of mitochondria-mediated oxidative phosphorylation (OXPHOS) in CD34CML cells within the primitive CML cell population are higher than those in normal undifferentiated hematopoietic cells; therefore, the inhibition of OXPHOS in CML-LSCs may be a potential cure for CML.
View Article and Find Full Text PDFNat Commun
October 2024
Center for Traditional Chinese Medicine and Gut Microbiota, Minhang Hospital, Fudan University, Shanghai, China.
Obesity and related diseases pose a major health risk, yet current anti-obesity drugs inadequately addressing clinical needs. Here we show AA005, an annonaceous acetogenin mimic, resists obesity induced by high-fat diets and leptin mutations at non-toxic doses, with the alpha subunit of the mitochondrial trifunctional protein (HADHA) as a target identified through proteomics and in vitro validation. Pharmacokinetic analysis shows AA005 enriches in adipose tissue, prompting the creation of adipose-specific Hadha-deficient mice.
View Article and Find Full Text PDFCells
October 2024
Laboratorio de Genómica, Instituto Nacional de Cancerología, Instituto Nacional Nacional de Cancerología, Av. San Fernando 22, Belisario Domínguez Secc 16, Tlalpan, Ciudad de México 14080, Mexico.
Unlabelled: LAH, an acetogenin from the Annonaceae family, has demonstrated antitumor activity in several cancer cell lines and in vivo models, where it reduced the tumor size and induced programmed cell death. We focused on the effects of LAH on mitochondrial dynamics, mTOR signaling, autophagy, and apoptosis in colorectal cancer (CRC) cells to explore its anticancer potential.
Methods: CRC cells were treated with LAH, and its effects on mitochondrial respiration and glycolysis were measured using Seahorse XF technology.
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