Integrated in silico and in vitro profiling of newly designed heterocyclic thiazolidinone targeting androgen-independent prostate cancer

Abstract

Objective: The current paper was to determine and assess the new heterocyclic thiazolidinone analogues as potential therapeutic agents in androgen-independent prostate cancer (AIPC) through the combined efforts of computational (in silico) and experimental (in vitro) designs in the androgen receptor.

Methods: A combined Density Functional Theory (DFT), molecular docking and pharmacokinetic prediction research strategy was used. First, the thiazolidinone derivatives were constructed, and the electronic properties and stability were examined with DFT. The interaction and binding affinity of the compounds with the androgen receptor were then studied by means of molecular docking. SwissADME and ADMETlab tools were used to predict drug-likeness, pharmacokinetic behaviour and toxicity profile. Lead compounds with promising results of computational analysis were prepared and subsequently tested with respect to cytotoxicity in PC-3 prostate cancer cell lines by the in vitro assays.

Results: The computational study showed that some of the thiazolidinone derivatives showed a high binding interaction with the androgen receptor. Of them, analogues containing halogen were found to possess improved receptor affinity and good pharmacokinetic characteristics. The structure-activity relationship was confirmed by the in vitro cytotoxicity studies of PC-3 cells, which demonstrated that these compounds had a higher biological activity due to their structure-activity relationship based on computational modelling.

Conclusion: The results demonstrate the therapeutic efficiency of electronically optimised derivatives of thiazolidinone regarding androgen-independent prostate cancer. The combined in silico in vitro strategy was found to be useful in expediting anticancer lead discovery, and it aids in using computational-experimental pipelines in rational drug design.