RESUMO
Benign Prostate Cancer (BPC), a prevalent condition predominantly affecting elderly males, manifests with voiding difficulties and urinary retention. A library of compounds from Trigonella foenum-graecum, commonly known as fenugreek was used in this study. We aimed to explore its potential anti-cancer effects by computationally assessing its inhibitory activity on the androgen receptor (AR). For in-silico drug assessment, we employed Maestro 12.8, part of the Schrödinger Suite, to identify the most promising candidates acting as androgen receptor antagonists in the treatment of BPC. Subsequently, 59 fenugreek compounds were retrieved from the PubChem database and subjected to molecular docking against the active site of the target protein, 1E3G. 100-nanosecond molecular dynamics (MD) simulations were performed to assess the stability and compactness of the AR-ligand complexes. Notably, the AR-kaempferol complex exhibited the least fluctuation within the AR active site throughout the simulation trajectory, followed by chlorogenic acid and the reference ligand, hydroxyflutamide. The MM/GBSA values revealed the compounds' maximum free binding energy (-103.3 ± 6, -87.4 ± 23, -68.5 ΔGbind) for chlorogenic acid, kaempferol, and hydroxyflutamide, respectively. These findings suggest their potential as promising leads for drug development. Further lead optimization and comprehensive studies on the top-ranked ligands identified in this investigation are warranted to advance their potential as therapeutic agents for BPC treatment.Communicated by Ramaswamy H. Sarma.
RESUMO
Available antimalarial drugs have been associated with numerous side effects, which include skin rashes and myelo-suppression. Therefore, it is of interest to explore compounds from natural source having drug-like properties without side effect. This study focuses on the screening of compounds from Cannabis sativa against malaria Plasmodium falciparum dihydrofolate reductase for antimalarial properties using Glide (Schrodinger maestro 2018-1). The result showed that phytochemicals from Cannabis sativa binds with a higher affinity and lower free energy than the standard ligand with isovitexin and vitexin having a glide score of -11.485 and -10.601 respectively, sophoroside has a glide score of -9.711 which is lower than the cycloguanil (co-crystallized ligand) having a glide score of -6.908. This result gives new perception to the use of Cannabis sativa as antimicrobial agent.
