Dual targeting in prostate cancer with phytoconstituents as a potent lead: a computational approach for novel drug discovery.

Prostate Cancer (PCa) is an abnormal cell growth within the prostate. This condition is the second most widespread malignancy in elderly males and one of the most frequently diagnosed life-threatening conditions. The Androgen receptor signaling pathway played a crucial role in the initiation and spread to increase the risk of PCa. Hence, targeting the AR receptor signaling pathway is a key strategy for a therapeutic plan for PCa. Our study focuses on recognizing potential inhibitors for dual targeting in PCa by using the in-silico approach. In this study, we target the two enzymes that are CYP17A1 (3RUK) and 5α-reductase (3G1R) responsible for PCa, with the help of phytoconstituents. The natural plant contains various phytochemical types produced from secondary metabolites and used as a medical treatment. The in-silico investigation of phytoconstituents and enzymes was done by approaching molecular docking, ADMET analysis, and high-level molecular dynamic simulation used to assess the stability and binding affinities of the protein-ligand complex. Some phytoconstituents, such as Peonidin, Pelargonidin, Malvidin and Berberine show complex has good molecular interaction with protein. The reliability of the docking scores was examined using a molecular dynamic simulation, which revealed that the complex remained stable throughout the simulation, which ranged from 0 to 200 ns. The selected hits may be effective against CYP17A1 (3RUK) and 5α-reductase (3G1R) (PCa) using a computer-aided drug design (CADD) method, which further enables researchers for upcoming in-vivo and in-vitro research, according to our in-silico approach.Communicated by Ramaswamy H. Sarma.

In silico approach towards polyphenols as targeting glucosamine-6-phosphate synthase for Candida albicans.

Candida albicans is one of the most common species of fungus with life-threatening systemic infections and a high mortality rate. The outer cell wall layer of C. albicans is packed with mannoproteins and glycosylated polysaccharide moieties that play an essential role in the interaction with host cells and tissues. The glucosamine-6-phosphate synthase enzyme produces N-acetylglucosamine, which is a crucial chemical component of the cell wall of Candida albicans. Collectively, these components are essential to maintain the cell shape and for infection. So, its disruption can have serious effects on cell growth and morphology, resulting in cell death. Hence, it is considered a good antifungal target. In this study, we have performed an in silico approach to analyze the inhibitory potential of some polyphenols obtained from plants. Those can be considered important in targeting against the enzyme glucosamine-6-phosphate synthase (PDB-2VF5). The results of the study revealed that the binding affinity of complexes theaflavin and 3-o-malonylglucoside have significant docking scores and binding free energy followed by significant ADMET parameters that predict the drug-likeness property and toxicity of polyphenols as potential ligands. A molecular dynamic simulation was used to test the validity of the docking scores, and it showed that the complex remained stable during the period of the simulation, which ranged from 0 to 100 ns. Theaflavins and 3-o-malonylglucoside may be effective against Candida albicans using a computer-aided drug design methodology that will further enable researchers for future in vitro and in vivo studies, according to our in silico study.Communicated by Ramaswamy H. Sarma.