No abstract

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.

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.

Prostate cancer (PCa) is the most common malignancy found in men and the second leading cause of cancer-related death worldwide. Castration-resistant prostate cancer (CRPC) is defined by PCa cells that stop responding to hormone therapy. Cytochrome P450 17α-hydroxylase/17,20-lyase (CYP17A1) plays a critical role in the biosynthesis of androgens in humans. Androgen signaling cascade is a principal survival pathway for prostate cancer cells, and androgen-deprivation therapy (ADT) remains the key treatment for patients marked with locally advanced and metastatic PCa cells. Available synthetic drugs have been reported for toxicity, drug resistance, and decreasing efficacy. Thus, the design of novel selective inhibitors of CYP17A1 lyase would help circumvent associated side effects and improve pharmacological activities. Therefore, we employed structural bioinformatics techniques via molecular docking; molecular mechanics generalized born surface area (MM-GBSA), molecular dynamics (MD) simulation, and pharmacokinetic study to identify putative CYP17A1 lyase inhibitors. The results of the computational investigation showed that the Prunus dulcis compounds exhibited higher binding energy than the clinically approved abiraterone acetate. The stability of the ligand with the highest binding affinity (Quercetin-3-o-rutinoside) was observed during MD simulation for 10 ns. Quercetin-3-o-rutinoside was observed to be stable within the active site of CYP17A1Lyase throughout the simulation period. The result of the pharmacokinetic study revealed that, these compounds are promising therapeutic agents. Collectively, this study proposed that bioactive compounds from P. dulcis may be potential selective inhibitors of CYP17A1Lyase in CRPC treatments.

Background The search for ideal drugs with absolute antiviral activity against SARS-CoV-2 is still in place, and attention has been recently drawn to natural products. Several molecular targets have been identified as points of therapeutic intervention. The targets used in this study include SARS-CoV-2 helicase, spike protein, RNA-dependent RNA polymerase, main protease, and human ACE-2. An integrative computer-aided approach, which includes molecular docking, pharmacophore modeling, and pharmacokinetic profiling, was employed to identify anthocyanins with robust multiple antiviral activities against these SARS-CoV-2 targets. Result Four anthocyanins (Delphinidin 3-O-glucosyl-glucoside, Cyanidin 3-O-glucosyl-rutinoside, Cyanidin 3-(p-coumaroyl)-diglucoside-5-glucoside), and Nasunin) with robust multiple inhibitory interactions were identified from a library of 118 anthocyanins using computer-aided techniques. These compounds exhibited very good binding affinity to the protein targets and moderate pharmacokinetic profiles. However, Cyanidin 3-O-glucosyl-rutinoside is reported to be the most suitable drug candidate with multiple antiviral effects against SARS-CoV-2 due to its good binding affinity to all five protein targets engaged in the study. Conclusions The anthocyanins reported in this study exhibit robust binding affinities and strong inhibitory molecular interactions with the target proteins and could be well exploited as potential drug candidates with potent multiple antiviral effects against COVID-19.