Identification of Promising Drug Candidates against Prostate Cancer through Computationally-Driven Drug Repurposing

Abstract

Prostate cancer (PC) is one of the most common types of cancer in males. Although early stages of PC are generally associated with favorable outcomes, advanced phases of the disease present a significantly poorer prognosis. Moreover, currently available therapeutic options for the treatment of PC are still limited, being mainly focused on androgen deprivation therapies and being characterized by low efficacy in patients. As a consequence, there is a pressing need to identify alternative and more effective therapeutics. In this study, we performed large-scale 2D and 3D similarity analyses between compounds reported in the DrugBank database and ChEMBL molecules with reported anti-proliferative activity on various PC cell lines. The analyses included also the identification of biological targets of ligands with potent activity on PC cells, as well as investigations on the activity annotations and clinical data associated with the more relevant compounds emerging from the ligand-based similarity results. The results led to the prioritization of a set of drugs and/or clinically tested candidates potentially useful in drug repurposing against PC.

Trends and Applications in Computationally Driven Drug Repurposing

“…Similar considerations arise from the study of Bernal et al [15], in which different types of ligand-based similarity estimations were performed between molecules with reported antiproliferative activity against prostate cancer (PC) cells and DrugBank compounds [16]. In this study, the performed analyses were also integrated with target-related activity data reported for PC, allowing the authors to identify 48 DrugBank compounds as potential repurposing or repositioning candidates, 5 of which have already been studied in clinical trials for prostate cancer.…”

Molecular docking and DFT study of 4-difluoromethyl pyrazole derivatives as cyclooxygenase-2 inhibitor

“…The primary factors examined in docking investigations encompassed binding energy [20], hydrogen bonding [21], hydrophobic interaction [22], and electrostatic interaction [23]. The results of this investigation provide valuable insights into the potential effectiveness and speci city of these derivatives, thereby offering guidance for subsequent experimental efforts in the realm of pharmaceutical development [24].…”