Tyrosinase Inhibitors: A Perspective.

Due to its integral role in the biosynthesis of melanin in all kingdoms of life, tyrosinase has become an extremely important target for inhibition in several sectors of research including agricultural and cosmetic research. Inhibitors of tyrosinase have made it to the market in the cosmetics industry, but their use has been limited due to conflicting efficacy and potential toxicity, which has led to several small molecules being removed from the market. Undaunted, researchers have continued to pursue tyrosinase inhibitors with varying degrees of success. These pursuits have built an impressive and rich library of research. This review is intended to provide a perspective of the past twenty years (2003-2023) of research on tyrosinase inhibitors by highlighting exemplar molecules and developments.

Structure-Activity Relationships of 7-Substituted Dimethyltyrosine-Tetrahydroisoquinoline Opioid Peptidomimetics.

The opioid receptors modulate a variety of biological functions, including pain, mood, and reward. As a result, opioid ligands are being explored as potential therapeutics for a variety of indications. Multifunctional opioid ligands, which act simultaneously at more than one type of opioid receptor, show promise for use in the treatment of addiction, pain, and other conditions. Previously, we reported the creation of bifunctional kappa opioid receptor (KOR) agonist/mu opioid receptor (MOR) partial agonist ligands from the classically delta opioid receptor (DOR) antagonist selective dimethyltyrosine-tetrahydroisoquinoline (Dmt-Tiq) scaffold through the addition of a 7-benzyl pendant on the tetrahydroisoquinoline ring. This study further explores the structure-activity relationships surrounding 7-position pendants on the Dmt-Tiq scaffold. Some analogues maintain a KOR agonist/MOR partial agonist profile, which is being explored in the development of a treatment for cocaine addiction. Others display a MOR agonist/DOR antagonist profile, which has potential to be used in the creation of a less addictive pain medication. Ultimately, we report the synthesis and in vitro evaluation of novel opioid ligands with a variety of multifunctional profiles.