Structure Based docking studies towards exploring potential anti-androgen activity of selected phytochemicals against Prostate Cancer

Abstract

Prostate cancer (PCa) is the second most common malignancy amongst men worldwide. Under PCa maintenance therapy drugs acting as antagonists/partial agonists of hormone receptors against the prostate tissue are used in clinical practices. Prominent drugs being Cyproterone acetate, Flutamide, Bicalutamide, they not only cause acute and long-term toxicity, but also develops drug resistance among patients. Our focus has been on phytochemicals which do not exhibit any cytotoxicity and have significant androgen receptor (AR) inhibition activity. As Protein- Ligand interactions play a key role in structure based drug design, so by using molecular docking, we screened 803 phytochemicals and investigated their binding affinity against AR. The three dimensional (3D) structure of AR was retrieved from Protein Data Bank, and docked with 3D Pubchem structures of 803 phytochemicals using Argus Lab. Molecular docking and drug likeness studies were made using ADMET properties while Lipinski’s rule of five was performed for the phytochemicals to evaluate their anti-prostate cancer activity. The results showed that Isobavachin exhibited best binding affinity of −13.73 kcal/mol with AR followed by Glabranin, Anthocyanin and Eriosemation. Our studies therefore reveal that these four phytochemicals could be promising candidates for further evaluation for PCa prevention or management.

Genipin inhibits the growth of human bladder cancer cells via inactivation of PI3K/Akt signaling

“…Natural phytochemicals have attracted increasing attention in cancer therapy due to their broad anticancer activity and low cytotoxicity in normal cells (14,18). Genipin has demonstrated anticancer properties in different types of cancers such as hepatocellular carcinoma (15) and colon cancer cells (16).…”

A Review on Protein Tyrosine Phosphatases - An Important Target for Various Diseases

“…Recent discoveries on plant phytochemicals against the PTP enzymes include Psidium guajava (Myrtaceae) leaf extracts which have one of the highest efficiency on the PTP enzyme active center inhibition to cure diabetes [63,64]. Natural plant phytochemicals such as curcumin as a ligand also showed high efficiency in binding with the active site of the PTP enzyme in prostate cancers through in silico docking analysis [65,66]. Compounds isolated from Sorbus commixta (Japanese flowering plant); lupeol and lupenone are also found to inhibit the PTP1B enzyme efficiently [67].…”

Non-specific protein modifications may be novel mechanism underlying bioactive phytochemicals

“…( 19 – 24 ) Recently, many have uncovered molecular targets of phytochemicals that directly mediate their biological and physiological functions. For example, Singh et al ( 25 ) conducted extensive screening of a total of 803 phytochemicals to examine their binding affinity for androgen receptor (AR) and found that the prenylated flavonoid isobavachin exhibited the highest affinity (–13.73 kcal/mol), followed by gabranin, athocyanin, and eiosemation. Also, β-secretase 1 (BACE1) has been noted to play a crucial role in development of Alzheimer’s disease.…”