ASSESSMENT OF ANTIPLASMODIAL POTENTIAL OF Phyllanthus amarus ESSENTIAL OIL AND METHANOL EXTRACT WITH In silico PREDICTION OF PARASITE MULTISTAGE BIOACTIVE COMPOUNDS
Main Article Content
Keywords
Malaria, Plasmodium falciparum, Phyllanthus amarus, Chloroquine, Artemisinin, γ-Sitosterol, Molecular docking
Abstract
Background: Malaria, predominantly caused by Plasmodium falciparum, remains a critical global health challenge exacerbated by increasing resistance to chloroquine and artemisinin-based combination therapies. Phyllanthus amarus, a medicinal plant widely used in Nigerian traditional medicine, offers promising phytochemicals for antimalarial drug development. Methods: Aerial parts were extracted via hydrodistillation and Soxhlet methods to obtain essential oil (1.7% w/w) and methanol extract (6.3% w/w). Chemical profiling using GC-MS identified major constituents including γ-sitosterol and quinoline derivatives. Antiplasmodial activity was evaluated against chloroquine-sensitive (3D7) and resistant (Dd2) strains using the SYBR Green I assay, while cytotoxicity was assessed on Vero cells. In silico molecular docking, ADMET profiling, and density functional theory (DFT) calculations were performed on identified bioactive compounds against PfDHFR, PfFAS, and PfEF1-α targets. Results: The essential oil demonstrated potent time-dependent inhibition (IC₅₀: 2.1–10.2 µg/mL at 96 h), low resistance indices (1.80–1.95), and high selectivity (SI up to 42.9). GC-MS profiling revealed 9,12,15-octadecatrien-1-ol (19.4%), 4-methoxy-3-nitrobenzyl alcohol ether (13.8%), and 8-aminoquinoline derivatives (12.5%) as major constituents in the oil, while the methanol extract contained 2′-hydroxy-6′-methoxyacetophenone acetate (15.5%) and glyoxal bis[(2,4-dinitrophenyl)hydrazone] (15.5%). In silico analysis identified γ-sitosterol as the most potent PfDHFR binder (−9.180 kCal/mol), outperforming pyrimethamine. The quinoline derivative demonstrated strong multi-target interactions and favourable drug-like properties. Conclusions: P. amarus extracts and their phytochemical constituents exhibit potent antiplasmodial activity, minimal cross-resistance, and multi-target potential. The quinoline derivative emerged as the most balanced lead compound, warranting further experimental validation. These findings support the development of P. amarus-derived compounds as novel antimalarial agents.