Analysis of plant-derived phytochemicals as anti-cancer agents targeting cyclin dependent kinase-2, human topoisomerase IIa and vascular endothelial growth factor receptor-2

Abstract

Cancer is caused by a variety of pathways, involving numerous types of enzymes, among them three enzymes: Cyclin dependent kinase-2 (CDK-2), Human topoisomerase IIα and Vascular Endothelial Growth Factor Receptor-2 (VEGFR-2) are three most common enzymes that are involved in the cancer development. Although many chemical drugs are available in the market, plant sources are known to contain a wide variety of agents that are known to possess anticancer activity. In this experiment, total thirty compounds were analysed against the mentioned enzymes using different tools of bioinformatics and in silico biology like molecular docking study, druglikeness property experiment, ADME/T test, PASS prediction and P450 site of metabolism prediction as well as DFT calculations to determine three best ligands that have the capability to inhibit the mentioned enzymes. Form the experiment, Epigallocatechin gallate was found to be the best ligand to inhibit CDK-2, Daidzein showed best inhibitory activities towards Human topoisomerase IIα and Quercetin was predicted to be the best agent against VEGFR-2. They were also predicted to be quite safe and effective agents to treat cancer. However, more in vivo and in vitro analysis are required to confirm their safety and efficacy in this regard.

Identification of the most potent acetylcholinesterase inhibitors from plants for possible treatment of Alzheimer’s disease: a computational approach

“…All of the 4 ligands were predicted to have significant gap energy representing their possibility to undergo a chemical reaction. However, among the four best selected ligands, coptisine, with its lowest gap energy, was predicted to have higher probability to undergo a chemical reaction [25,117] (Table 9 and Fig. 3).…”

“…By simulating the interaction between ligand and receptor in the computer software, the docking system assigns scoring functions to the bound ligands which reflect their binding affinity. The lower docking score represents the greater binding affinity and vice-versa [24,25]. The current study was designed to predict the best ligands among 50 selected phytochemicals with potential anti-AChE activities based on the molecular docking analysis (Table 2).…”

Computational Exploration of Phytochemicals as Potent Inhibitors of Acetylcholinesterase Enzyme in Alzheimer’s Disease

“…XP G Score is generated in the IFD experiment, which is an empirical scoring function that estimates the ligand binding free energy. The lowest value of XP G Score is considered as the best value and is always appreciable [71, 72, 73, 74] . In the MM-GBSA study, based on the ΔG Bind score, XP G Score value and IFD score, coptisine can be considered as the best ligand molecule among the selected three ligands.…”

Phytochemicals Target Growth Factor Receptors to Control Cancer: An In Silico Study

“…Due to the roles growth factor receptors play in the development and progression of cancer, it is necessary to develop suitable drug candidates that can effectively inhibit growth factors at the sites of receptors with little or no effects. Binding a nity between ligands and receptors is determined by the binding energy, the lower the energy the higher the binding a nity [9]. For this purpose, 50 bioactive compounds were screened against ERRB2/HER2, ERRB3/HER3, VEGFR-2, VEGFR-3 and FGFR-2.…”

“…In some cancer, these receptors are often overexpressed leading to uncontrolled proliferation and differentiation, [8] their ampli cation activates both inherent and acquired resistance to cancer treatments. Overexpression of HER-2 gene were found in breast, bladder, lung and glial carcinomas, HER-3 gene in aggressive metastatic breast, ovarian, lung, gastric, invasive urothelial bladder and endometrial carcinomas, VEGFR1-3genes found in large number of tumors like bladder, colon, breast, lung, brain, prostate, gastric, kidney, thyroid and ovarian cancer cells, FGFR-2 gene in gastric, breast, endometrial and lung carcinomas [6,9]. The role of these receptors in cancer progression has made them a necessary therapeutic target for effective cancer therapy.…”