ArticleBritish journal of pharmacology2010
16alpha-Hydroxycleroda-3,13 (14)Z-dien-15,16-olide from Polyalthia longifolia: a safe and orally active antileishmanial agent.
Article in British journal of pharmacology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 70 citations in OpenAlex.
- A Novel Sesterterpenoid, Petrosaspongin and γ-Lactone Sesterterpenoids with Leishmanicidal Activity from Okinawan Marine Invertebrates.Marine drugs · 2024Article
- Antileishmanial evaluation of triazole-butenolide conjugates: design, synthesis,RSC medicinal chemistry · 2023Article
- Antileishmanial Effects of Bunium Persicum Crude Extract, Essential Oil, and Cuminaldehyde on Leishmania Major: In Silico and In Vitro Properties.Acta parasitologica · 2023Article
- Novel Aporphine- and Proaporphine-Clerodane Hybrids Identified from the Barks of TaiwanesePharmaceuticals (Basel, Switzerland) · 2022Article
- Clerodane Diterpenoids from an Edible PlantMolecules (Basel, Switzerland) · 2021Article
- Phytochemicals fromMolecules (Basel, Switzerland) · 2021Review
- 16-Hydroxycleroda-3,13-dien-15,16-olide Induces Apoptosis in Human Bladder Cancer Cells through Cell Cycle Arrest, Mitochondria ROS Overproduction, and Inactivation of EGFR-Related Signalling Pathways.Molecules (Basel, Switzerland) · 2020Article
- A Review of the Antimalarial, Antitrypanosomal, and Antileishmanial Activities of Natural Compounds Isolated From Nigerian Flora.Frontiers in chemistry · 2020Review
- Multi-target mode of action of a Clerodane-type diterpenoid from Polyalthia longifolia targeting African trypanosomes.Scientific reports · 2018Article
- 16-Hydroxycleroda-3,13-dien-15,16-olide induces anoikis in human renal cell carcinoma cells: involvement of focal adhesion disassembly and signaling.OncoTargets and therapy · 2018Article
- Therapeutic effect of ursolic acid in experimental visceral leishmaniasis.International journal for parasitology. Drugs and drug resistance · 2017Article
- Recent developments in drug discovery for leishmaniasis and human African trypanosomiasis.Chemical reviews · 2014Review
- Induction of mitochondrial dysfunction and oxidative stress in Leishmania donovani by orally active clerodane diterpene.Antimicrobial agents and chemotherapy · 2014Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
background and purposeNew antileishmanials from natural products are urgently needed due to the emergence of drug resistance complicated by severe cytotoxic effects. 16alpha-Hydroxycleroda-3,13 (14)Z-dien-15,16-olide (Compound 1) from Polyalthia longifolia was found to be a potential antileishmanial and non-cytotoxic, as evidenced by long-term survival (>6 months) of treated animals. This prompted us to determine its target and, using molecular modelling, identify the interactions responsible for its specific antileishmanial activity. EXPERIMENTAL APPROACH: In vitro activity of compound was assessed using intracellular transgenic green fluorescent protein-stably expressed Leishmania donovani parasites. In vivo activity and survival of animals post-treatment were evaluated in L. donovani-infected hamsters. Known property of clerodane diterpenes as potent human DNA topoisomerase inhibitors led us to evaluate the inhibition of recombinant L. donovani topoisomerase I using relaxation assay. Mode of cell death induced by Compound 1 was assessed by phosphotidylserine exposure post-treatment. Molecular modelling studies were conducted with DNA topoisomerase I to identify the binding interactions responsible for its activity. KEY
resultsBioassay-guided fractionation led to isolation of Compound 1 as a non-cytotoxic, orally active antileishmanial. Compound 1 inhibited recombinant DNA topoisomerase I which, ultimately, induced apoptosis. Molecular docking studies indicated that five strong hydrogen-bonding interactions and hydrophobic interactions of Compound 1 with L. donovani DNA-topoisomerase are responsible for its antileishmanial activity. CONCLUSIONS AND IMPLICATIONS: The data reveal Compound 1 is a potent and safe antileishmanial. The study further exploited the structural determinants responsible for its non-cytotoxic and potent activity, to raise the feasibility of specifically targeting the target enzyme responsible for its activity through rational drug design.
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