Microwave‐assisted synthesis and biological evaluation of new thiazolylhydrazone derivatives as tyrosinase inhibitors and antioxidants

Abstract

In this work, we have synthesized a series of 2‐thiazolylhydrazone derivatives (1–27) and investigated their biological activities as tyrosinase inhibitors and antioxidants. Some compounds showed potent tyrosinase inhibitory activities and 4‐(2‐(2‐(1‐(4‐Aminophenyl)ethylidene)‐hydrazinyl)thiazol‐4‐yl) phenol (26) showed more potent inhibitory effect than the standard tyrosinase inhibitor kojic acid (IC50: 9.8 μM vs. 23.6 μM). Compounds 2, 14, and 26 exhibited high antioxidant activities in 2,2‐diphenyl‐1‐picrylhydrazyl (DPPH) and 2,2′‐azinobis (3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS) assays. The structure–activity relationship (SAR) indicated that the substitutions of bromine, hydroxyl group, and amino groups cause great effect to the inhibition effect against tyrosinase. The mechanism and kinetic studies demonstrated that the inhibitory effect of compound 26 on the tyrosinase by acting as the reversible and uncompetitive inhibitor. Docking studies suggests that compound 26 interacts strongly with mushroom tyrosinase via hydrogen bonding.

Synthetic Curcumin Analogues Present Antiflavivirus Activity In Vitro with Potential Multiflavivirus Activity from a Thiazolylhydrazone Moiety

“…Similarly, modifications of substituents over aromatic moieties in curcumin analogues could favour and enhance antiviral activity, as shown in the optimization of E protein inhibitors against DENV-2 [54]. Thiazolylhydrazone substituents have also shown other biological activities in the past, including antibacterial [64], antifungal [65], as well as anti-inflammatory [66] and antioxidant [67]. Additionally, the synthetic curcumin analogues with thiazolylhydrazone moieties proposed in this work could even be supported by the targets predicted from inhibitors' similarities, which were also available in different active compounds with designed thiazolylhydrazone moieties assessed by Jadav et al 2015 [54] against DENV-2.…”

Synthesis, Biological Activity and Molecular Docking Studies of Novel Sulfonate Derivatives Bearing Salicylaldehyde

“…Recently, various natural and synthetic tyrosinase inhibitors have been investigated as cosmetic and therapeutic agents. Several synthetic tyrosinase inhibitors such as arbutin, hydroquinone, and kojic acid are still controversial for biosafety fears owing to their side effects [24] . Thus, investigating new and effective tyrosinase inhibitors with low side effects has been the subject of many studies.…”

“…Several synthetic tyrosinase inhibitors such as arbutin, hydroquinone, and kojic acid are still controversial for biosafety fears owing to their side effects. [24] Thus, investigating new and effective tyrosinase inhibitors with low side effects has been the subject of many studies. Until now, many compounds have been addressed for their potent tyrosinase inhibitions, such as flavones, [25] peptides, [26] Schiff bases, [27] and sulfonamide chalcones.…”

Synthesis, Characterization, ADMET prediction, and Molecular Docking Studies of Novel Coumarin Sulfonate Derivatives

“…Tyrosinase inhibitors of synthetic compounds like arbutin, kojic acid, and hydroquinone have been still discussed as safe from a biosafety point of view due to their side effects. In this context, investigating effective tyrosinase inhibitors with fewer side effects has been still scanned by researchers (Zhang, et al, 2020). For example, peptides (Hariri, et al, 2020), benzothiazole (Korkmaz and Bursal, 2022a), flavones, (Arroo, et al, 2020), and Schiff bases (Alyar, et al, 2019), were investigated for tyrosinase inhibition effects.…”