Design, Synthesis and In-Silico Studies of Novel Chalcones as Anti-Prostate Cancer and Cathepsin B Inhibitors

In the present study a series of novel N-(4-3-(pheny)-1-prop-2-en-1-one phenyl) benzamide derivatives (5a-p) were synthesized, characterized and evaluated for their anti-prostate cancer activities against PC-3 prostate adenocarcinoma cell line using the SRB method. The cathepsin B inhibition potential was further tested by the using enzyme-linked immunosorbent assay. The furyl derivative 5p was the most active candidate, (IC50 = 5.597μΜ), against prostate cancer cell line, PC-3. This derivative also demonstrated 50.4% reduction in concentration of cathepsin B, additionally, compounds 5b and 5m showed 53.2 and 56.6% reduction in concentration of cathepsin B, respectively. In conclusion, compounds 5b, 5m and 5p showed good activity both as antiproliferative and as inhibitors of Cathepsin B production. Moreover, a pharmacophore model was constructed, a QSAR study was carried out where a model was successfully built from which the physicochemical parameters were correlated to the activity. This developed QSAR model was found statistically significant and had good predictive power. Furthermore, molecular docking studies of the active derivatives were also carried out, where they were found to maintain the essential key interactions, specially with the cysteine residue, Cys29.