Design and synthesis of novel dihydropyridine- and benzylideneimine-based tyrosinase inhibitors.

Tyrosinase (TYR) inhibitors are very significant as they inhibit enzyme tyrosinase activity, and its inhibition is vital for skin care, anticancer medication, and antibrowning of fruits and vegetables. This work presents a novel and economical route for the preparation of new synthetic tyrosinase inhibitors using amlodipine . The novel conjugates were designed, synthesized, and characterized by spectroscopic analyses, including Fourier transform infrared and low- and high-resolution mass spectroscopy. The purified compound was refluxed with various aldehydes and ketones for 5-8 h in methanol at 60°C-90°C. This research modified the drug in a step-by-step manner to develop therapeutic properties as a tyrosinase inhibitor. The structures of synthesized ligands were established based on spectral and analytical data. The synthesized compounds were screened against tyrosinase enzyme. Kojic acid was taken as standard. All the prepared compounds have good inhibition potential against the enzyme tyrosinase. Compounds , , , and depicted excellent antityrosinase activity. Compound , with an IC value of 5.34 ± 0.58 µM, is as potent as the standard kojic acid (IC 6.04 ± 0.11 µM), standing out among all synthesized compounds . The studies of the conjugates were evaluated via . Compound showed a binding affinity score of 8,999 and an atomic contact energy (ACE) value of -219.66 kcal/mol. The structure-activity relationship illustrated that the presence of dihydropyridine nuclei and some activating groups at the ortho and para positions of the benzylideneimine moiety is the main factor for good tyrosinase activity. The compound could be used as a lead compound for drug modification as a tyrosinase inhibitor for skin care, anticancer medication, and antibrowning for fruits and vegetables.