In-Silico Screening of Flavonoids targeted for Death Receptors in Cancer by Using Hex Molecular Docking

Abstract

Objective: Docking is one of the major tools in the drug development process, here we have selected certain flavonoid molecules such as Formononetin, Tangeritin, Myricetin and Kaempferol and we docked against Death Receptors (DRs) for the prevention of cancer progression. Materials and Methods: In this study, Protein Ligand Docking, we have used HEX as a Docking Software. Receptor structure was obtained from Protein Data Bank (PDB) while the ligand is drawn by using the Chem Draw Software and docking was done according to the specified parameters. Results: All the investigatory molecules except tangeritin (DR5 -212.2; DR 2 -231.1) showed higher energy values on the Death Receptor 5 (Formononetin DR5 -197.8) which states, these flavonoid molecules are having higher affinity and steric compatibility to Death Receptor 5, where DR5 mediates the TRAIL mediated apoptosis. Tangeritin molecule shows higher energy values at DR2 -231.1, it may mediate its effect through the Fas apoptotic path. The Docked molecules are viewed with the help of chimera software to discover the interaction of molecules with the receptors. Conclusion:From the present study, it is confirmed that these investigatory molecules showed a predictable effect over Death Receptors, and further studies will be carried out with ADME/T (Absorption, Distribution, Metabolism, Elimination, Toxicity) Tool. Phone no: 09894699234Email: vishnuvj24@gmail.com DOI: 10.5530/jyp.2017.9.33 This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.Vishnuvarthan et al.: Docking Studies for Flavonoids.

Formononetin: A Review of Its Anticancer Potentials and Mechanisms

“…Despite the abundant evidence of formononetin-induced intrinsic apoptosis pathway, there is still no report on the apoptotic effect of formononetin mediated through the extrinsic pathways via stimulation of death receptors on the cell surface, such as tumor necrosis factor receptor (TNFR) superfamily. Nevertheless, a recent in silico study, which investigated the interactions between formononetin and death receptors, revealed that formononetin could be a potential molecule in inducing extrinsic apoptosis pathway (Vishnuvarthan et al, 2017). The study showed that formononetin displayed high affinity and steric compatibility to death receptor 5, which could be activated to mediate the TNF-related apoptosis-inducing ligand (TRAIL)-induced apoptosis (Walczak et al, 1997).…”

Docking study of selected citrus flavonoids towards exploring the potential anti estrogen activity

“…The MM/GBSA analysis of selected compound Pubchem ID 68077 has shown binding energy of 34.60. In recent study by Vishnuvarthan et al, 2017 reported that the in silico screening of flavonoids such as formononetin, tangeritin, myrecitin and kaempferol were used as targets against death receptors for prevention of cancer progression [38]. The Protein-ligand interactions of the stable docked HER alpha and tangeritin complex was visualized with ligand interaction diagram shown in Fig.…”

Matteucinol combined with temozolomide inhibits glioblastoma proliferation, invasion, and progression: an in vitro, in silico, and in vivo study

“…These results suggested that these two molecules may act together increasing their potential. Another in silico study showed the affinity of some flavonoids to death receptors, including TNFR1 ( 37 ). Therefore, our data indicated that Mat-TMZ can initiate caspase cascade activation through the activation of the TNFR1 signaling pathway, leading to induction of both intrinsic and extrinsic apoptotic pathways.…”