Design, Synthesis, Pharmacological Activities, Structure-Activity Relationship, and In Silico Studies of Novel 5-Substituted-2-(morpholinoimino)-thiazolidin-4-ones.

This study is aimed to synthesize morpholine- and thiazolidine-based novel 5-(substituted)benzylidene)-2-(morpholinoimino)-3-phenylthiazolidin-4-ones (3-26) and characterized by molecular spectroscopy. The synthesized compounds were subjected to antioxidant activity with anticholinesterase, tyrosinase, and urease inhibition activities and evaluated the structure-activity relationship (SAR) of enzyme inhibition activities. Compound 11 was found to be the most active antioxidant. In anticholinesterase inhibition, compound 12 (IC50: 17.41 ± 0.22 µM) was the most active against AChE, while compounds 3-26 ( except 3, 8, and 17) showed notable activity against BChE. Compounds 17 (IC50: 3.22 ± 0.70 mM), 15 (IC50: 5.19 ± 0.03 mM), 24 (IC50: 7.21 ± 0.27 mM), 23 (IC50: 8.05 ± 0.11 mM), 14 (IC50: 8.10 ± 0.22 mM), 25 (IC50: 8.40 ± 0.64 mM), 26 (IC50: 8.76 ± 0.90 mM), and 22 (IC50: 9.13 ± 0.55 mM) produced higher tyrosinase inhibition activity. In urease inhibition activity, compounds 20 (IC50: 16.79 ± 0.19 µM), 19 (IC50: 18.25 ± 0.50 µM), 18 (IC50: 20.24 ± 0.77 µM), 26 (IC50: 21.51 ± 0.44 µM), 25 (IC50: 21.70 ± 0.06 µM), and 24 (IC50: 22.49 ± 0.11 µM) demonstrated excellent activities. Besides, the molecular docking study was applied to better understand the inhibitory mechanism between (1-26) compounds and enzymes at the molecular level. According to the results of this study, the synthesized compounds exhibited a better binding affinity toward these enzymes compared to the positive control. Further, molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) binding free energy and molecular dynamics (MD) simulation analyses were performed for AChE with compound 26, which showed high inhibitory activity in silico and in vitro studies. In conclusion, novel morpholine and thiazolidine-based derivative compounds may be pharmacologically effective agents for AChE, BChE, tyrosinase, and urease enzymes.

Design, in Silico Studies and Biological Evaluation of New Chiral Thiourea and 1,3-Thiazolidine-4,5-dione Derivatives.

In this study, new chiral thiourea and 1,3-thiazolidine-4,5-dione derivatives were synthesized, it was aimed to evaluate the various biological activities and molecular docking of these compounds. Firstly, the new thioureas (1-16) were obtained by reacting 1-naphthylisothiocyanate with different chiral amines. Then, the chiral thioureas were cyclized with oxalyl chloride to obtain 1,3-thiazolidine-4,5-dione derivatives (17-32). All compounds were evaluated with several in vitro antioxidant and enzyme inhibition activities. Compound 30 was the most active compound against AChE, with a value of IC50 =8.09±0.58 µM. On the other hand, all compounds were tested in silico absorption, distribution, metabolism, and excretion (ADME) assays to better understand their bioavailability. These physicochemical properties, pharmacokinetics, and drug-likeness of all compounds were calculated using SwissADME. Furthermore, according to molecular docking analyses compound 30 exhibited significant binding affinities for all enzymes. Based on our overall observations, compound 30 could be recommended as a potential lead for the therapuetic of Alzheimer's.

Synthesis and evaluation of the antioxidant and anti-tyrosinase activities of thiazolyl hydrazone derivatives and their application in the anti-browning of fresh-cut potato.

Tyrosinase is a key enzyme in the biosynthesis of melanin, which is responsible for the browning of foods as well as many skin disorders. In order to develop new anti-browning agents with dual antioxidant and anti-tyrosinase capacities, a series of 30 thiazolyl hydrazone derivatives were synthesized. Among the molecules prepared, 6 and 30 were found to be the most potent tyrosinase inhibitors with IC50 values ​​comparable to that of kojic acid. Interestingly, 6 also has the highest radical scavenging activity among the prepared molecules. The inhibition kinetics study indicated that 6 is a non-competitive inhibitor while 30 inhibits tyrosinase competitively. The anti-browning assay of fresh-cut potato slices revealed that 6 and 30 are potent anti-browning agents with a capacity as high as kojic acid. The mechanisms of free radical scavenging and tyrosinase inhibition have been fully investigated in silico using computational kinetics, molecular docking, and molecular dynamics simulations.