Amentoflavone and methyl hesperidin, novel lead molecules targeting epitranscriptomic modulator in acute myeloid leukemia: in silico drug screening and molecular dynamics simulation approach.

Autor: Manna S; Department of Bioscience, JIS University, 81, Nilgunj Road, Agarpara, Kolkata, 700109, West Bengal, India., Samal P; Department of Bioscience, JIS University, 81, Nilgunj Road, Agarpara, Kolkata, 700109, West Bengal, India., Basak R; Department of Bioscience, JIS University, 81, Nilgunj Road, Agarpara, Kolkata, 700109, West Bengal, India., Mitra A; Department of Bioscience, JIS University, 81, Nilgunj Road, Agarpara, Kolkata, 700109, West Bengal, India., Roy AK; Department of Bioscience, JIS University, 81, Nilgunj Road, Agarpara, Kolkata, 700109, West Bengal, India., Kundu R; Department of Bioscience, JIS University, 81, Nilgunj Road, Agarpara, Kolkata, 700109, West Bengal, India., Ahir A; Department of Bioscience, JIS University, 81, Nilgunj Road, Agarpara, Kolkata, 700109, West Bengal, India., Roychowdhury A; Department of Bioscience, JIS University, 81, Nilgunj Road, Agarpara, Kolkata, 700109, West Bengal, India. amlan.roychowdhury@jisuniversity.ac.in., Hazra D; Department of Bioscience, JIS University, 81, Nilgunj Road, Agarpara, Kolkata, 700109, West Bengal, India. ditipriya.hazra@jisuniversity.ac.in.
Jazyk: angličtina
Zdroj: Journal of molecular modeling [J Mol Model] 2022 Dec 16; Vol. 29 (1), pp. 9. Date of Electronic Publication: 2022 Dec 16.
DOI: 10.1007/s00894-022-05407-1
Abstrakt: Introduction: M 6 A modification in transcriptome is critical in regulating different cellular processes, including cancer. In human beings, METTL3 is the major m 6 A writer that works in association with METTL14, an accessory protein. Extensive study revealed that cancer progression for acute myeloid leukemia, gastric cancer, colorectal cancer, hepatocellular carcinoma, and lung cancer is directly contributed by irregular expression of METTL3.
Objective: Targeting METTL3 has opened a new window in the development of novel inhibitors/drugs.
Methods: In this study, commercially available natural compounds were randomly screened to avoid the bias of screening small molecules on the basis of structural similarity. From 810 compounds that were screened, 80 commercially available compounds were showing better score when compared with the existing substrate/substrate-analogue and the inhibitor bound crystal structures in terms of docking score and binding energy calculation.
Results and Conclusion: Among this pool of compounds, the best seven small molecules have been selected and further validated by different computational tools like binding energy calculation, molecular dynamics simulation, ADME analysis, and toxicity prediction. The novel hits found in this study can function as lead compounds which can be developed into inhibitors as well as drugs, specific against METTL3.
(© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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