Prostate cancer is the second most common disease in men and the sixth leading cause of death from cancer globally, with 20 million men expected to be affected by 2024 thus considered as chronic illness which requires immediate attention. As an androgen-dependent illness that relies on the androgen receptor for development and progression, inhibition of the androgen receptor can lead to a therapeutic solution, hence serving as a vital therapeutic target. This study focused on the computational analysis of the inhibitory potentials of Vitis vinifera, a reported plant with anti-cancer properties, against androgen receptor employing molecular docking, ADMET studies, Binding energy study, pharmacophore modeling, and molecular dynamics simulation approaches. After the investigation, it was determined that 5 compounds: cis-piceid, cis-astrigin, gallocatechin, phlorizin, and trans-polydatin, might be possible androgen receptor inhibitors since they had higher docking scores and ADMET qualities than compared standards, with cis-piceid being the best-predicted inhibitor.

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Background β-catenin is an important unit of the Wnt/β-catenin signaling pathway, a conserved process involving several physiological activities, encompassing differentiation and cell proliferation, etc. The dysfunction or mutation in β-catenin causing the initiation and advancement of various neoplasm types, including colorectal cancer, breast cancer, etc., has been reported. Therefore, β-catenin is a therapeutic target. Hence, designing new inhibitors targeted against β-catenin will prevent cancerous cells’ involvement and eliminate the diseases. Studies showed that Vitis vinifera, a well-known grape species, contains different phytochemical substances, including aromatic acids, flavonoids, phenolic compounds, proanthocyanins, etc. V.vinifera exerts different anticancer properties such as apoptosis, cell proliferation, cell cycle arrest, and inhibition in cancerous cells. Structural bioinformatics methods, including molecular docking, molecular mechanics generalized Born surface area (MM/GBSA), absorption, distribution, metabolism, excretion studies (ADMET), and pharmacophore modeling approach, were used to determine the potential β-catenin inhibitors from V.vinifera bioactive compounds. Result Cis-astringin, rutin, caftaric acid, trans-caftaric acid, procyanidin B3, cis-Miyabenol C, and ampelopsin H are shown to be suitable inhibitors against β-catenin due to their binding affinity and interaction with the amino acids residues at the binding sites of β-catenin compared to Food and Drug Administration (FDA) approved drugs leucovorin Calcium and Xeloda prescribed to cure colorectal cancer. Conclusions This study suggests that V. vinifera could be a good plant source for compounds that might treat cancer by inhibiting the Wnt/β-catenin signaling pathway.

O-GlcNAcylation is a nutrient-sensing post-translational modification process. This cycling process involves two main proteins; the O-linked N-acetylglucosamine transferase (OGT) catalyzing the addition, and the glycoside hydrolase OGA (O-GlcNAcase) catalyzing the removal of the O-GlCNAc moiety on nucleocytoplasmic proteins. This process is necessary for various important cellular functions. The O-linked N-acetylglucosamine transferase (OGT) gene is responsible for the production of the OGT protein. Several studies have shown the overexpression of this protein to have biological implications in metabolic diseases like cancer and diabetes mellitus (DM). In this study, we retrieved a total of 159 SNPs with clinical significance from the SNPs database and we probed the functional effects, stability profile, and evolutionary conservation of these to determine their fit for this research. We then identified 7 SNPs (G103R, N196K, Y228H, R250C, G341V, L367F, and C845S) with predicted deleterious effects across the four tools used (PhD-SNPs, SNPs&Go, PROVEAN, and PolyPhen2). Proceeding with this, we used ROBETTA, a homology modeling tool, to model the proteins with these point mutations and carried out a structural bioinformatics method – molecular docking – using the Glide model of the Schrodinger Maestro suite. We used a previously reported inhibitor of OGT, OSMI-1, as the ligand for these mutated protein models, and as a result, very good binding affinities and interactions were observed between this ligand and the active site residues within 4Å of OGT. We conclude that these mutation points may be used for further downstream analysis as drug targets for the treatment of diabetes mellitus.