Synthesis, in Vitro Cholinesterase Inhibition, Molecular Docking, DFT, and ADME Studies of Novel 1,3,4-Oxadiazole-2-Thiol Derivatives.

A series of 1,3,4-oxadiazole-2-thiol derivatives bearing various alkyl or aryl moieties were designed, synthesized, and characterized using modern spectroscopic methods to yield 17 compounds (6a-6q) that were screened for acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes in the search for 'lead' compounds for Alzheimer's disease treatment (AD). The compounds 6q, 6p, 6k, 6o, and 6l showed inhibitory capability against AChE and BChE, with IC50 values ranging from 11.73±0.49 to 27.36±0.29 µM for AChE and 21.83±0.39 to 39.43±0.44 µM for BChE, inhibiting both enzymes within a limited range. The SAR ascertained that the substitution of the aromatic moiety had a profound effect on the AChE and BChE inhibitory potential as compared to the aliphatic substitutions which were supported by the molecular docking studies. The drug-likeness of the most synthesized compounds was confirmed by in silico ADME investigations. These results were additionally supplemented by the molecular orbital analysis (HOMO-LUMO) and electrostatic potential maps got from DFT calculations. ESP maps expose that on all structures, there are two potential binding sites conquered by the most positive and most negative districts.

Organocatalyzed and mechanochemical solvent-free synthesis of novel and functionalized bis-biphenyl substituted thiazolidinones as potent tyrosinase inhibitors: SAR and molecular modeling studies.

Eluding the involvement of solvents in organic synthesis and introducing environment friendly procedures can control environmental problems. A facile and an efficient solvent free mechanochemical method (grinding) is achieved to synthesize novel bis-biphenyl substituted thiazolidinones using non-toxic and cheap N-acetyl glycine (NAG). Organocatalytic condensation of a series of Schiff's bases bearing different substituents with thioglycolic acid produces a variety of thiazolidinones derivatives in good to excellent yield. In vitro inhibition studies against mushroom tyrosinase of these thiazolidinone analogues revealed that many of them possessed good to excellent tyrosinase inhibition at low micro-molar concentrations. In particular, six compounds exhibited potent inhibitory potential with IC50 values ranging from 0.61 ± 0.31 to 21.61 ± 0.11 µM as compared with that of standard kojic acid (IC50 6.04 ± 0.11 µM). Further molecular docking studies revealed that the thiazolidinones moiety plays a key role in the inhibition mechanism by well fitting into the enzyme bounding pocket.

Enzyme inhibition, antioxidant and antibacterial potential of vasicine isolated from Adhatoda vasica Nees.

Vasicine (1) was isolated from the ethanolic extract of Adhatoda vasica Nees (Acanthaceae) and the structure was confirmed using spectroscopic techniques. Acetylcholine esterase, trypsin, DPPH inhibition potential and FRAP assay were carried out using in vitro models. The results showed 38.4 ± 1.2% and 37.4 ± 1.1% activity in acetylcholine and trypsin inhibition assays respectively. The compound (1) exhibited significant DPPH inhibition activity (70.4 ± 1.3%, IC(50) = 212.3 ± 1.9 µM). A dose dependant behavior of vasicine (1), was indicated in the FRAP assay. Antibacterial activity was checked according to agar well diffusion assay and results revealed that vasicine (1) showed moderate activity.

3-Benzyl-5-benzyl-idene-2-sulfanylidene-1,3-thia-zolidin-4-one.

In the title mol-ecule, C(17)H(13)NOS(2), the essentially planar thia-zole ring (r.m.s deviation 0.005 Å) forms dihedral angles of 16.85 (8)° and 75.02 (8)° with the phenyl rings. The dihedral angle between the two phenyl rings is 61.95 (9)°.