ArticlePloS one2020
Antileishmanial compounds from Connarus suberosus: Metabolomics, isolation and mechanism of action.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 19 citations in OpenAlex.
- Flavonoids in the treatment ofFrontiers in pharmacology · 2025Pooled it
- Taxonomic and functional inferences of cultivable endophytic fungi in two endemic Cerrado plants: dominance of Diaporthe across contrasting host phenologies.Folia microbiologica · 2026Article
- Botanical Authenticity of Miraruira Sold in the Amazonas State, Brazil, Based on Chemical Profiling Using DI-MS and Chemometric Analyses.Plants (Basel, Switzerland) · 2025Article
- Exploring the Potential of Malvidin and Echiodinin as Probable Antileishmanial Agents Through In Silico Analysis and In Vitro Efficacy.Molecules (Basel, Switzerland) · 2025Article
- Metabolomic Strategies to Improve Chemical Information from OSMAC Studies of Endophytic Fungi.Metabolites · 2023Article
- The Search for Putative Hits in Combating Leishmaniasis: The Contributions of Natural Products Over the Last Decade.Natural products and bioprospecting · 2021Review
- Challenges, Advances and Opportunities in Exploring Natural Products to Control Arboviral Disease Vectors.Frontiers in chemistry · 2021Review
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Leishmaniasis is a disease impacting public health worldwide due to its high incidence, morbidity and mortality. Available treatments are costly, lengthy and toxic, not to mention the problem of parasite resistance. The development of alternative treatments is warranted and natural products demonstrate promising activity. This study investigated the activity of Connarus suberosus extracts and compounds against Leishmania species. Several C. suberosus extracts were tested against L. amazonensis promastigotes. Active and inactive extracts were analyzed by UHPLC-MS and data evaluated using a metabolomics platform, revealing an unknown neoflavonoid (connarin, 3), isolated together with the pterocarpans: hemileiocarpin (1) and leiocarpin (2). The aforementioned compounds (1-3), together with the benzoquinones: rapanone (4), embelin (5) and suberonone (6) previously isolated by our group from the same species, were tested against: (i) L. amazonensis and L. infantum promastigotes, and (ii) L. amazonensis intracellular amastigotes, with the most active compound (3) also tested against L. infantum amastigotes. Cytotoxicity against murine peritoneal macrophages was also investigated. Compounds 2 and 3 presented an IC50 33.8 μM and 11.4 μM for L. amazonensis promastigotes; and 44.3 μM and 13.3 μM for L. infantum promastigotes, respectively. For L. amazonensis amastigotes, the IC50 of 2 was 20.4 μM with a selectivity index (SI) of 5.7, while the IC50 of 3 was 2.9 μM with an SI of 6.3. For L. infantum amastigotes, the IC50 of 3 was 7.7 μM. Compounds 2 and 3 presented activity comparable with the miltefosine positive control, with compound 3 found to be 2-4 times more active than the positive control, depending on the Leishmania species and form. The extracts and isolated compounds showed moderate toxicity against macrophages. Compounds 2 and 3 altered the mitochondrial membrane potential (ΔΨm) and neutral lipid body accumulation, while 2 also impacted plasma membrane permeabilization, culminating in cellular disorder and parasite death. Transmission electron microscopy of L. amazonensis promastigotes treated with compound 3 confirmed the presence of lipid bodies. Leiocarpin (2) and connarin (3) demonstrated antileishmanial activity. This study provides knowledge of natural products with antileishmanial activity, paving the way for prototype development to fight this neglected tropical disease.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.