Development of resistance against the frontline anti-malarial drugs has created an alarming situation, which requires intensive drug discovery to develop new, more effective, affordable and accessible anti-malarial agents. Inspired by their ethnobotanical reputation for being effective against febrile diseases, antiplasmodial potential of ethyl acetate extracts (EAE) and methanol extracts (ME) of 17 medicinal plants collected from the Eastern Ghats of South India and Buchpora, North India were explored against Plasmodium falciparum in vitro using the SYBR Green assay. The results were validated both by confirmation that the fall in fluorescence signal was not due to quenching effects mediated by phytochemical extracts and by Giemsa-stained microscopy. Using EAE or ME, promising antiplasmodial activity (IC50 Pf3D7 ≤ 20 μg/ml), was seen in Aerva lanata (Whole aerial parts-EAE), Anisomeles malabarica (Leaf-EAE), Anogeissus latifolia (bark-EAE), Cassia alata (leaves-EAE), Glycyrrhiza glabra (root-EAE), Juglans regia (seed-ME), Psidium guajava (leaf-ME and EAE) and Solanum xanthocarpum (Whole aerial parts-EAE). EAEs from leaves of Couroupita guianensis, Euphorbia hirta, Pergularia daemia, Tinospora cordifolia and Tridax procumbens as also ME from Ricinus communis (leaf and seed) showed good antiplasmodial activity (Pf 3D7 IC50 21 - 40 μg/ml). Moderate activity (Pf 3D7 IC50: 40–60 μg/mL) was shown by the leaf EAEs of Cardiospermum halicacabum, Indigofera tinctoria and Ricinus communis while the remaining extracts showed marginal (Pf 3D7 IC50 60 to >100 μg/ml) activities. The promising extracts showed good resistance indices (0.41 – 1.4) against the chloroquine resistant INDO strain of P. falciparum and good selectivity indices (3 to > 22.2) when tested against the HeLa cell line. These results provide validity to the traditional medicinal usage of some of these plants and further make a case for activity-guided purification of new pharmacophores against malaria.

A series of β-benzoylstyrene derivatives of acridine (4a–r) have been synthesized and characterized using IR, ¹H NMR and Mass Spectroscopy. All the compounds were screened for intraerythrocytic in vitro antimalarial activity against Chloroquine-sensitive (3D7) & Chloroquine-resistant (Dd2) strains of Plasmodium falciparum using the SYBR Green I fluorescence assay. Cytotoxicity study was performed against the HeLa cell line using the MTT assay. Compounds 4c, 4d, and 4l are most potent with IC₅₀ in the range of 0.30–0.52 μM against the 3D7 strain and 0.15–0.32 μM against the Dd2 strain. The results revealed that antimalarial potency and good resistance indices were not at the cost of safety since the most potent compounds have turned out to have promising therapeutic indices in the range of 80–520.