Protozoan Neglected Tropical Diseases (NTDs) Target Inhibition of Alkaloids from Croton linearis Jacq Leaves: A Molecular Docking and ADMET Approach
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11160%2F25%3A10505926" target="_blank" >RIV/00216208:11160/25:10505926 - isvavai.cz</a>
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=01OuXbBJW5" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=01OuXbBJW5</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.3390/ph18111715" target="_blank" >10.3390/ph18111715</a>
Alternative languages
Result language
angličtina
Original language name
Protozoan Neglected Tropical Diseases (NTDs) Target Inhibition of Alkaloids from Croton linearis Jacq Leaves: A Molecular Docking and ADMET Approach
Original language description
Background/Objectives: Neglected tropical diseases (NTDs) caused by protozoan parasites such as Trypanosoma cruzi, Trypanosoma brucei, Leishmania spp., and Plasmodium falciparum remain a global health challenge due to limited therapies and increasing drug resistance. Natural products provide diverse scaffolds for antiparasitic drug discovery. This study aimed to investigate the multitarget inhibitory potential of alkaloids isolated from Croton linearis Jacq. against validated protozoan enzymes. Methods: Eighteen alkaloids were virtually screened against 17 molecular targets relevant to protozoan parasites. Protein-ligand docking simulations were performed using crystallographic structures of enzymes, including Cyp51, DHFR-TS, PTR1, AD-kinase, and DHODH. Predicted interactions were analyzed to identify hydrogen bonds, hydrophobic contacts, and pi-pi stacking with key residues in the active sites. Results: Several alkaloids exhibited high binding affinities, in some cases surpassing co-crystallized ligands. Reticuline, norsalutaridine, laudanosine, and jacularine consistently showed the strongest activity, with docking scores ranging from -8.0 to -9.3 kcal/mol across multiple targets. Notably, norsalutaridine displayed the highest predicted affinity for L. infantum Cyp51, while reticuline showed strong binding to T. cruzi DHFR-TS and L. major PTR1. Conclusions: The study highlights the potential of C. linearis alkaloids as multitarget inhibitors against protozoan parasites. These compounds represent promising lead candidates for the development of antiparasitic agents, while emphasizing the value of natural product scaffolds for neglected disease drug discovery. The findings also support the future exploration of semisynthetic derivatives to optimize activity and selectivity.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30104 - Pharmacology and pharmacy
Result continuities
Project
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Continuities
S - Specificky vyzkum na vysokych skolach<br>I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2025
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Pharmaceuticals
ISSN
1424-8247
e-ISSN
1424-8247
Volume of the periodical
18
Issue of the periodical within the volume
11
Country of publishing house
CH - SWITZERLAND
Number of pages
23
Pages from-to
1715
UT code for WoS article
001623771100001
EID of the result in the Scopus database
2-s2.0-105022866236