Abstract
The lymphomas are a heterogeneous group of cancer of the lymphocytes and the lymphatic system and accounts for up to 3% of all malignancies.1 Most of the drugs currently used for the treatment of lymphoma produce various side effects, hence in this study, we focus on natural compounds, obtained from the medicinal plant Vitex negundo, which exhibits selective toxicity against cancer cells. The objective of this research was to formulate the binding energies and interaction of selected phytochemicals present in the medicinal plant Vitex negundo2 against anaplastic lymphoma kinase protein, which is overexpressed in an anaplastic large cell lymphoma.3, 4,5 The structure of mutant human anaplastic lymphoma kinase protein was retrieved from the Protein Data Bank (PDB ID:4ANL ) and the 3D chemical structure of the phytochemicals present in the medicinal plant Vitex negundo was obtained from the PubChem database. Molecular docking study was performed for these natural compounds to evaluate and analyze their anti-lymphoma-cancer activity. A total of 16 compounds present in Vitex negundo, based on a comprehensive literature survey was selected for this molecular screening. Molecular docking analysis was carried out by Molegro Virtual Docker software, to screen the 16 chosen compounds and rank them according to their binding affinity towards the site of interaction of the oncoprotein, anaplastic lymphoma kinase. Out of the 16 screened phytocompounds, only 4 compounds showed promising interactions against the oncoprotein ALK (4ANL). 6’-p-hydroxybenzoyl mussaenosidic acid exhibited a very good binding with a molecular docking score of -127.723 kcal/mol, ranking first among the compounds screened. This was followed by Betulinic acid, Viridiflorol and protocatechuic acid with molecular docking scores of -95.596 kcal/mol, -76.1648 kcal/mol and -63.0854 kcal/mol and - respectively. The docking scores from the above study shows that the phytocompounds present in Vitex negundo extract exhibits an effective inhibitory effect against anaplastic lymphoma kinase protein that is over expressed in lymphoma.
Highlights
Anaplastic lymphoma kinase is an enzyme that is active during the embryonic nervous system development of humans, but slowly loses its activity over the course of postnatal life[1]
anaplastic lymphoma kinase (ALK) was originally identified as an fusion oncogene nucleophosmin (NPM)-ALK resulting from a t (2,5) chromosomal translocation in ALCL .The fusion oncogene NPM-ALK is implicated in the pathogenesis of ALCL as it is detected in approximately 75% of all ALK-positive ALCL (6)
Interaction site Prediction The association of anaplastic lymphoma kinase (ALK) with anaplastic large cell lymphoma has been well characterized by various studies
Summary
Anaplastic lymphoma kinase is an enzyme that is active during the embryonic nervous system development of humans, but slowly loses its activity over the course of postnatal life[1] This enzyme is prone to various kinds of mutations notably chromosomal fusion. There are twenty such fusion proteins documented that are known to be involved predominantly in the pathogenesis of neuroblastoma, anaplastic large cell lymphomas and non- small cell lung cancer[2]. Few of these ALK inhibitors like Crizotinib (12) have advanced to the level of clinical trials[5,6]; Crizotinib recently gained FDA approval for ALK-positive cancers It is used in the treatment of EML4-ALK-positive NSCLC but like any other drugs it is known to cause side effects. A number of ALK antagonists have appeared of which a set of novel and potent tetracyclic derivatives (6, 6-Dimethyl11-oxo-6, 11- dihydro-5-H-benzo (b) carbazoles) (13–15) have been chosen for our present studies[7]
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