In Silico Docking Studies of Gallic Acid Structural Analogues as BCL-Xl Inhibitor in Cancer

Abstract

Objective: Apoptosis, or programed cell death, forms an important part of the cellular regulation machinery. The Bcl-2 protein family, comprising proapoptotic and antiapoptotic members, forms an important part of the cells internal apoptotic pathway. Overexpression of the antiapoptotic members of the family in a number of cancer cell lines renders them immune to apoptosis and the ability to survive under conditions of cellular stress. Inhibition of the antiapoptotic members of the Bcl-2 family like Bcl-XL is, therefore, an interesting target for the development of anticancer therapy. Methods:The structure of antiapoptotic Bcl-XL receptor (1YSG) was taken from PDB database. The 23-dimensional structure of gallic acid analogs was designed. The Lipinski properties of gallic acid analogs were calculated using molsoft. Docking studies have been carried out through Autodock 4.0 software.Results: Molecular docking analysis with gallic acid and their structural analogs showed propyl gallate, benzyl gallate, diallyl gallate, phenyl ethyl gallate, and allyl gallate are more interactive and binding strongly than gallic acid at active site of Bcl-XL. Conclusion:Further these five compounds should be considered as potential candidates for Bcl-XL inhibitor.

2441 Interleukin-1b and Cyclooxygenase-2 Proinflammation Analysis and in Silico Docking Nuclear Factor Kappa B on Endometriosis Cell Culture Given Heptyl Gallate and Octyl Gallate Treatment

“…The effect of heptyl gallate and octyl gallate on primary endometriosis cells toward pro-inflammatory cytokines IL-1β in this study showed Based on the results of in silico docking analysis, the docking energy (binding energy score/∆G) of gallic acid compounds, heptyl gallate and octyl gallate as ligand against protein NFkB targets respectively −7.66 kkal/mol, −7.68 kkal/mol and −7.98 kkal/mol. ∆G shows the strength of the ligand affinity with the target protein, in which the higher of the negative ∆G value the interaction and conformation between ligand and protein will be more constant and stable [19]. In this study, the octyl gallate showed a stronger and more stable affinity toward NFKB than heptyl gallate and gallic acid.…”

Molecular Docking, Molecular Dynamics, and in Silico Toxicity Prediction Studies of Coumarin, N-Oxalylglycine, Organoselenium, Organosulfur, and Pyridine Derivatives as Histone Lysine Demethylase Inhibitors

“…5). Ligands 11,15, and, to a lesser extent, 12, showed strong interactions with the enzyme active site.…”

“…Molecular docking simulations can be used to quickly screen a database of chemical compounds for potential drug molecules. Indeed, many studies have been performed in which molecular docking was used to discover potential anticancer agents, including the screening of potent (peroxisome proliferator-activated receptor-gamma) agonists from natural resources [12], the screening of potential BRCA1 inhibitors [13], docking studies on the interactions of eriodictyol with apoptotic proteins [14], and the development of gallic acid structural analogs as BCL-XL inhibitors [15].…”

Molecular docking, ADMET profiling of gallic acid and its derivatives (N-alkyl gallamide) as apoptosis agent of breast cancer MCF-7 Cells

“… 15 According to in silico study, gallic acid and its derivatives (alkyl ester) can be BRAF inhibitor of colorectal cancer, 16 as well as inhibitor of the anti-apoptosis protein Bcl-xL in breast cancer. 17 , 18 In addition, gallic acid derivative compounds (N-alkyl gallamide) have strong cytotoxic activity on MCF7 breast cancer cells, and colorectal cancer cells, HCT 116. 19 , 20 This study aims to design gallic acid derivative compounds (N-alkyl Gallamide), analyze molecular modeling of target proteins associated with breast cancer, and determine the ADMET profile of these compounds as apoptosis agents of MCF-7 breast cancer cells.…”