Synthesis and Molecular Docking of New Bis-Thiazolidinone-Based Chalcone Analogs as Effective Inhibitors of Acetylcholinesterase and Butyrylcholinesterase.
Chem Biodivers
; 19(10): e202200323, 2022 Oct.
Article
em En
| MEDLINE
| ID: mdl-35997224
ABSTRACT
This work reports the convenient strategy for the synthesis of bis-thiazolidinone based chalcone analogs (1-20) from readily available thiosemicarbazide hydrochloride, ammonium thiocyanate and benzaldehyde. All the newly afforded bis-thiazolidinone based chalcone analogs (1-20) were screened inâ
vitro for their acetylcholinesterase and butyrylcholinesterase inhibition profile. It was noteworthy, that all the synthetic analogs (except analogs 10, 12 and 14, which are found to be inactive) showed moderate to good inhibitory potentials on screening against acetylcholinesterase having range of inhibitory with IC50 values from 0.070±0.050 to 7.60±0.10â
µM, and similarly for butyrylcholinesterase with range IC50 values from 0.10±0.050â
µM to 10.70±0.20â
µM, respectively as compared to standard Donepezil inhibitor (IC50 =2.16±0.12â
µM), (IC50 =4.5±0.11â
µM).Among the series, the analogs with hydroxy group showed superior inhibitory potentials against acetylcholinesterase and butyrylcholinesterase enzymes. Therefore, analog 20 (IC50 =0.070±0.050â
µM), (IC50 =0.10±0.050â
µM) bearing trihydroxy substitutions on ortho-, meta- and para-position of both rings A and B was found to be the most active inhibitor of acetylcholinesterase and butyrylcholinesterase enzymes among the current synthesized series (1-23). Analog 19 (IC50 =0.15±0.050â
µM), (IC50 =0.20±0.050â
µM) bearing dihydroxy substitutions on ortho- and meta-position of both ring A and ring B was identified as the second most potent inhibitor against both these enzymes. Interestingly, the compound (16) (IC50 =1.50±0.10â
µM against AChE) has a better selectivity index (2.60) than standard Donepezil drug (2.083) for AChE over BuChE. The different types of spectroscopic techniques such as HR-EI-MS, 1 H- and 13 C- NMR were used to confirm the structure of all the newly synthetics analogs. To find structure-activity relationship, molecular docking studies were carried out to understand the binding mode of active inhibitors with active site of enzymes and results supported the experimental data.
Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Chalcona
/
Chalconas
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article