Antiproliferative Efficacy of Kaempferol on Cultured Daudi Cells: An In Silico and In Vitro Study

Abstract

There is always a constant need to develop alternative or synergistic anticancer drugs with minimal side effects. One important strategy to develop effective anticancer agents is to investigate potent derived compounds from natural sources. The present study was designed to determine antiproliferative activity of Kaempferol using in silico as well as in vitro study. Docking was performed using human GCN5 (hGCN5) protein involved with cell cycle, apoptosis, and glucose metabolism. Cell viability and cytotoxicity on Daudi cells were evaluated by trypan blue and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays in a dose and time dependent manner, respectively. The compound inhibited the proliferation and growth of the Daudi cells, through induced cell death. The pure compound proved lead inhibitors of cell proliferation, thus manifesting significant antiproliferative activity. The docking results revealed that Kaempferol exhibited binding interaction to hGCN5 protein. Further, molecular dynamics using the dock pose of hGCN5-Kaempferol complex were performed to understand the basic structural unit which lead to inefficiency in binding and, therefore, pronounced instability and its possible consequences of reduced binding affinity. The data obtained in this study indicates that Kaempferol is a promising compound leading to inhibition of Daudi cell growth and proliferation.

Pharmacophore-based virtual screening of catechol-o-methyltransferase (COMT) inhibitors to combat Alzheimer’s disease

“…The structure has a depth of resolution 2.8 Å and contains 216 amino acids, ligand 3, 5-dinitrocatechol (DNC), cofactor S-adenosyl L- methionine (SAM), and magnesium ion (Mg +2 ). Removal of water molecules, energy minimization (Kumar et al, 2015; Modi et al, 2016) were performed with the help of the standard steepest decent conjugate method in YASARA (Parmar, Patel, Highland, Pandya, & George, 2016). The 36 ligands from ZINC database (Irwin et al, 2012) were docked in the place of DNC, located at the binding site of COMT.…”

“…A molecular dynamics simulation study was undertaken by using YASARA (Krieger & Vriend, 2015) with AMBER03 force field (Parmar et al, 2016) for 8 docked complexes. The 3a7e protein was cleaned, hydrogens were added; water molecules were removed.…”

“…Steepest descent minimization was used and simulation continued by 1 ns. The following molecular dynamics simulation steps were performed: temperature of 298 K, pressure at 1 bar, coulomb electrostatics at a cut off of 7.86, 0.9% NaCl, solvent density 0.997, pH 7.0, 1-fs time steps, periodic boundaries, all atoms mobile (Parmar et al, 2016). The average structures were determined from the simulations and were used to calculate the RMSDs and RMSFs for the respective model.…”

A Novel Ruthenium‐Fluvastatin Complex Downregulates SNCG Expression to Modulate Breast Carcinoma Cell Proliferation and Apoptosis via Activating the PI3K/Akt/mTOR/VEGF/MMP9 Pathway

“…On the basis of this data, the current research uses molecular docking, a widely used bioinformatics technique to evaluate how the molecule of ruthenium-fluvastatin binds and interacts with the SNCG target proteins. These in silico methodologies aid towards classifying drug targets through computer-assisted designing that helps to (i) envision specific active sites for evaluating target structures, (ii) produce potential molecules that identify the target, (iii) determine their comparative receptor binding affinities, and (iv) modify molecules to optimize binding abilities [38]. AutoDock is one of the many software programs that consists of a series of automatic docking techniques developed to evaluate how molecules attach to a particular targeted protein with a preordained arrangement [39].…”

A Novel Ruthenium Fluvastatin Complex Downregulates SNCG Expression to Modulate Breast Carcinoma Cell Proliferation and Apoptosis Via Activating PI3K/Akt/mTOR/VEGF/ MAP Kinase Pathway

“…On the basis of this data, the current research uses molecular docking, a widely used bioinformatics technique to evaluate how the molecule of ruthenium uvastatin binds and interacts with the SNCG target proteins. These in silico methodologies aids towards classifying drug targets through computer-assisted designing that help to i) envision speci c active sites for evaluating target structures ii) produce potential molecules that identify the target iii) determine their comparative receptor binding a nities and iv) modify molecules to optimize binding abilities (45). Autodoc is one of many softwares that consists of a series of automatic docking techniques developed to evaluate how molecules attach to a particular targeted protein with a preordained arrangement (46).…”