Background:
The major attention has been received by the natural products in the
prevention of diseases due to their pharmacological role.
Objective:
The major focus of the study was to search for highly potential anti-cancer compounds
from marine Streptomyces sp. VITJS4 (NCIM No. 5574).
Methods:
Cytotoxic assay was examined by MTT assay on HepG2 cells. Bioassay-guided fractionation
of the ethyl acetate extract from the fermented broth led to the isolation of the compound. The
lead compound structure was elucidated by combined NMR and MS analysis, and the absolute configuration
was assigned by extensive spectroscopic analysis.
Results:
On the basis of spectroscopic data, the compound was identified as 1, 2
benzenedicarboxylic acid, mono 2-ethylhexyl (BMEH). The compound exhibited in vitro anticancer
potential against liver (HepG2) cancer cells. Based on the flow cytometric analysis, it was evident
that the BMEH was also effective in arresting the cell cycle at G1 phase. Further, the Western blotting
analysis confirmed the down-regulation of Bcl-2 family proteins, and activation of caspase-9
and 3. The molecular docking and dynamics simulation were performed to reveal the activity of the
compound over a time period of 10ns. From the molecular dynamics studies, it was found that the
stability and compactness were attained by the protein by means of the compound interaction.
Conclusion:
This study highlights our collaborative efforts to ascertain lead molecules from marine
actinomycete. This is the first and foremost report to prove the mechanistic studies of the purified
compound 1, 2-benzene dicarboxylic acid, mono(2-ethylhexyl) ester isolated from marine Streptomyces
sp.VITJS4 against HepG2 cells.
Dasatinib–SIK2 Binding Elucidated by Homology Modeling, Molecular Docking, and Dynamics Simulations
