Evaluation of Polar Substituted Schiff Bases and 1,2,3-Triazole Hybrids as Anticancer Agents

Polar substituted Schiff bases and 1,2,3-triazole hybrids (2–6) were successfully synthesized by Schiff base condensation reaction between the previously synthesized triazole 1 and series of polar substituted amines. The chemical structures of the hybrids were confirmed using spectroscopies (NMR and FTIR), CHN elemental analysis and single-crystal x-ray diffraction analysis. The compounds were evaluated for their antiproliferative activity against two cancer cells, PC3 (prostate) and MCF7 (breast) cell lines, using the alamarBlue assay method, and camptothecin was employed as a standard. All the compounds exhibited good activity for the proliferation of the cancer cell lines compared to the standard, and their activity is concentration-dependent. Compounds 1, 2, 4 and 5 exhibited good caspase activity with relevant dosages that inhibited 50% (IC₅₀) in prostate cancer cells. All the compounds exhibited high binding affinity for human 3-alpha hydroxysteroid dehydrogenase type 3 (PDB ID: 4xo6) and Androgen receptor (PDB ID: 2Q7K) inhibitors compared to the reference anticancer drug (camptothecin). Structure–activity relationships (SARs) of the tested compounds are in good agreement with DFT and molecular docking studies. ADMET analysis was used to predict the pharmacokinetics, pharmacodynamics and toxicology of the compounds, and it proved that the compounds exhibited desirable physicochemical properties for drug likeness.