Combinatorial chemistry & high throughput screening · 2022
In vitro Evaluation and Molecular Dynamics, DFT Guided Investigation of Antimalarial Activity of Ethnomedicinally used Coptis teeta Wall.
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Goswami Ashis Kumar, Sharma Hemanta Kumar, Gogoi Neelutpal, Kashyap Ankita, Gogoi Bhaskarjyoti
Аннотация
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.
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.