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Background: Malaria is caused by different species of Plasmodium; among which P. falciparum is the most severe. Coptis teeta is an ethnomedicinal plant of enormous importance for tribes of northeast India., Objective: In this study, the antimalarial activity of the methanol extracts of Coptis teeta was evaluated in vitro and lead identification was carried out via in silico study., Methods: On the basis of the in vitro results, in silico analysis by application of different modules of Discovery Studio 2018 was performed on multiple targets of P. falciparum taking into consideration some of the compounds reported from C. teeta., Results: The IC50 of the methanol extract of Coptis teeta was reported to be 0.08 μg/ml in 3D7 strain and 0.7 μg/ml in Dd2 strain of P. falciparum. From the docking study, noroxyhydrastatine was observed to have better binding affinity in comparison to chloroquine. The binding of noroxyhydrastinine with dihydroorotate dehydrogenase was further validated by molecular dynamics simulation and was observed to be significantly stable in comparison to the co-crystal inhibitor. During simulations, it was observed that noroxyhydrastinine retained the interactions, giving strong indications of its effectiveness against the P. falciparum proteins and stability in the binding pocket. From the Density-functional theory analysis, the bandgap energy of noroxyhydrastinine was found to be 0.186 Ha, indicating a favorable interaction., Conclusion: The in silico analysis as an addition to the in vitro results provides strong evidence of noroxyhydrastinine as an antimalarial agent., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Development of resistance by the malaria parasite Plasmodium falciparum has created challenges in the eradication of this deadly infectious disease. Hence newer strategies are adopted to combat this disease and simultaneously, new lead/hit identification is going on worldwide to develop new chemotherapeutic agents against malaria., Objective: In this study, 44 flavonoids found mainly in the fruit juice of Citrus species having traditional use in malaria-associated fever were selected for in silico multiple-target directed screening against three vital targets of the parasite namely dihydroorotate dehydrogenase (PfDHODH), dihydrofolate reductase thymidine synthase (PfDHFR-TS) and plasma membrane P-type cation translocating ATPase (PfATP4) to find out new lead molecule(s)., Methods: The in silico screening was carried out using different protocols of the Biovia Discovery Studio 2018 software and Network analyzer plugin of Cytoscape 3.6.0 followed by in vitro screening of the best lead., Results: After screening, CF8 or luteolin was found to have good binding affinity against PfDHODH and PfATP4 with -CDocker energy 42.2719 and 33.1447 with respect to their cocrystal ligands. These findings were also supported by structure-based pharmacophore, DFT (Density Functional Theory) study and finally by in vitro screening of the lead with IC50 values of 8.23 μm and 12.41 μm against 3D7 (chloroquine-sensitive) and RKL-9 (chloroquine-resistant) strain of P. falciparum, respectively., Conclusion: Our study found a moderately active lead molecule with the predicted mode of action which can be utilized to design some new derivatives with more safety and efficacy by targeting the two enzymes., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)