Synthesis, In Silico Studies, and Antioxidant and Tyrosinase Inhibitory Potential of 2-(Substituted Phenyl) Thiazolidine-4-Carboxamide Derivatives

Abstract

Heterocyclic nuclei have shown a wide variety of biological activities, highlighting their importance in drug discovery. Derivatives of 2,4-subsituted thiazolidine have a structural similarity with the substrates of tyrosinase enzymes. Hence, they can be used as an inhibitor to compete against tyrosine in the biosynthesis of melanin. This study is focused on design, synthesis, biological activities, and in silico studies of thiazolidine derivatives substituted at positions 2 and 4. The synthesized compounds were evaluated to determine the antioxidant activity and tyrosine inhibitory potential using mushroom tyrosinase. The most potent tyrosinase enzyme inhibitor was compound 3c having IC50 value 16.5 ± 0.37 µM, whereas compound 3d showed maximum antioxidant activity in a DPPH free radical scavenging assay (IC50 = 18.17 µg/mL). Molecular docking studies were conducted using mushroom tyrosinase (PDB ID: 2Y9X) to analyze binding affinities and binding interactions of the protein–ligand complex. Docking results indicated that hydrogen bonds and hydrophobic interactions were mainly involved in the ligand and protein complex. The highest binding affinity was found to be −8.4 Kcal/mol. These results suggest that thiazolidine-4-carboxamide derivatives could serve as lead molecules for development of novel potential tyrosinase inhibitors.

In Vitro and In Vivo Biological Evaluation of Indole-thiazolidine-2,4-dione Derivatives as Tyrosinase Inhibitors

“…The absorbance changes in the mixture containing 5w (0, 4, 8, and 16 µM), tyrosinase (66.7 U/mL), and L-DOPA (2, 4, 6, and 8 mM) were recorded, respectively. The data were analyzed using Lineweaver-Burk plots [36].…”

Synthesis, Anti-Tyrosinase Activity, and Spectroscopic Inhibition Mechanism of Cinnamic Acid–Eugenol Esters

“…White soild; yield 42% (the crude was purified using a mixture of PE/EtOAc 60:1); mp: 343.2-343.3 • C; 1 H NMR (500 MHz, CDCl 3 ) δ 7.88 (d, J = 16.0 Hz, 1H, Ar-H), 7.68 (s, 1H, Ar-H), 7.68 (s, 1H, CH), 7.68 (s, 1H, Ar-H), 7.68 (s, 1H, Ar-H), 7.03 (d, J = 7.9 Hz, 1H, Ar-H), 6.83 (d, J = 1.9 Hz, 1H, Ar-H), 6.81 (dd, J = 8.0, 1.9 Hz, 1H, Ar-H), 6.75 (d, J = 16.0 Hz, 1H, CH), 5.98 (td, J = 16.8, 6.7 Hz, 1H, CH), 5.16-5.06 (m, 2H, CH 2 ), 3.83 (s, 3H, OCH 3 ), 3.41 (d, J = 6.7 Hz, 2H, CH 2 ); 13 7.02 (d, J = 7.9 Hz, 1H, Ar-H), 6.81 (d, J = 1.9 Hz, 1H, Ar-H), 6.79 (dd, J = 7.9, 1.9 Hz, 1H, Ar-H), 6.70 (s, 1H, Ar-H), 6.68 (d, 1H, Ar-H), 6.44 (d, J = 15.8 Hz, 1H, CH), 5.98 (td, J = 16.8, 6.7 Hz, 1H, CH), 5.17-5.07 (m, 2H, CH 2 ), 3.83 (s, 3H, OCH 3 ), 3.39 (d, J = 6.8 Hz, 2H, CH 2 ), 3.04 (s, 6H, CH 3 , CH 3 ); 13…”

“…Tyrosinase (EC 1.14.18.1), which is one kind of copper-containing metalloenzyme, widely exists in nature animals and plants [ 1 , 2 , 3 ]. Tyrosinase plays crucial roles in mediating the production of melanin pigment via two steps [ 4 , 5 , 6 , 7 , 8 ]. In the melanin process, tyrosinase monophenolase firstly catalyzes the hydroxylation of L-tyrosine to yield L-DOPA, which is further oxidized into o -dopaquinone by tyrosinase diphenolase ( Figure 1 ) [ 9 , 10 , 11 , 12 ].…”

Inhibition mechanism investigation of quercetagetin as a potential tyrosinase inhibitor

“…Tyrosinase has been confirmed to be involved in the synthesis of melanin ( Li et al, 2023 ; Hassan et al, 2023 ; Li J. et al, 2021 ). The first reaction process is monophenolase activity, in which L-tyrosine is hydroxylated into L-dopa and the second reaction process is diphenolase activity, in which L-dopa is subsequently oxidized into dopaquinone ( Djafarou et al, 2023 ; Lee et al, 2023 ; Zargaham et al, 2023 ). In the organism, melanin acts crucial roles to protect the skin from UV radiation ( Lu et al, 2023a ; Znajafi et al, 2023 ).…”