In silico antimalarial bioprospecting of neem (Azadirachta indica) quinine-derivative alkaloids
Malaria, driven by the protozoan Plasmodium spp. and transmitted by Anopheles mosquitoes, remains a significant global health threat. With the emergence of chloroquine-resistant malaria, alternative treatments derived from natural compounds are pressing. This study explores neem (Azadirachta indica)...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Pontificia Universidad Javeriana
2025-04-01
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| Series: | Universitas Scientiarum |
| Subjects: | |
| Online Access: | https://revistas.javeriana.edu.co/index.php/scientarium/article/view/38480 |
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| Summary: | Malaria, driven by the protozoan Plasmodium spp. and transmitted by Anopheles mosquitoes, remains a significant global health threat. With the emergence of chloroquine-resistant malaria, alternative treatments derived from natural compounds are pressing. This study explores neem (Azadirachta indica), a Southeast Asian plant, as a source of antimalarial agents. A Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) analysis of a neem leaf extract identified 184 compounds, of which five quinone-derivative compounds were subject to in silico screening against three Plasmodium falciparum virulence proteins: Purine nucleoside phosphorylases (PNP), dihydroorotate dehydrogenase (DHODH), and erythrocyte membrane protein 1 (EMP1). Among these five compounds (A-E), compound C emerged as the top candidate, ranking highly in molecular stability (FMO energy gaps), drug-likeness (Lipinski’s Rule of 5), bioavailability, and synthetic accessibility. Compound C also
exhibited strong binding affinity to PNP and DHODH in molecular docking and dynamics simulations and ranked among the top three for binding free energy in MM/PBSA calculations. However, it lacked predicted antiprotozoal activity in PASS screening, though it shared key enzyme targets with established antimalarial drugs. These findings nominate compound C as a promising candidate for further research as a potential antimalarial agent. |
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| ISSN: | 0122-7483 |