Novel Thiosemicarbazone Derivatives: In Vitro and In Silico Evaluation as Potential MAO-B Inhibitors

Abstract

MAO-B inhibitors are frequently used in the treatment of neurodegenerative diseases such as Parkinson’s and Alzheimer’s. Due to the limited number of compounds available in this field, there is a need to develop new compounds. In the recent works, it was shown that various thiosemicarbazone derivatives show hMAO inhibitory activity in the range of micromolar concentration. It is thought that benzofuran and benzothiophene structures may mimic structures such as indane and indanone, which are frequently found in the structures of such inhibitors. Based on this view, new benzofuran/benzothiophene and thiosemicarbazone hybrid compounds were synthesized, characterized and screened for their hMAO-A and hMAO-B inhibitory activity by an in vitro fluorometric method. The compounds including methoxyethyl substituent (2b and 2h) were found to be the most effective agents in the series against MAO-B enzyme with the IC50 value of 0.042 ± 0.002 µM and 0.056 ± 0.002 µM, respectively. The mechanism of hMAO-B inhibition of compounds 2b and 2h was investigated by Lineweaver–Burk graphics. Compounds 2b and 2h were reversible and non-competitive inhibitors with similar inhibition features as the substrates. The Ki values of compounds 2b and 2h were calculated as 0.035 µM and 0.046 µM, respectively, with the help of secondary plots. The docking study of compound 2b and 2h revealed that there is a strong interaction between the active sites of hMAO-B and analyzed compound.

Design, synthesis, in silico and biological evaluations of novel polysubstituted pyrroles as selective acetylcholinesterase inhibitors against Alzheimer’s disease

“…Compounds containing N-heterocyclic skeletons are known to exhibit various biological and medicinal activities [30][31][32][33][34] . Among these compounds, pyrrole derivatives are generally shown to have several biological activities as antioxidant 35 , antifungal 36 , antituberculosis 37 , anti-inflammatory 38 , analgesic 39 , antidiabetic 40 and anticancer 41 agents. Some examples of pharmaceutical compounds with pyrrole ring skeletons are shown in Fig.…”

Hydrazones and Thiosemicarbazones Targeting Protein-Protein-Interactions of SARS-CoV-2 Papain-like Protease

“…The compound interaction hotspots, including the interactions of the polar thiocarbonyl moiety, resemble the modular composition of other previously described thiocarbazone lead compounds ( Osmaniye et al, 2021 ). While thiosemicarbazones currently attract significant interest as anticancer agents ( Baruffini et al, 2020 ), they also show antiviral activity against smallpox and other viruses ( Kune, 1964 ; Rogolino et al, 2015 ).…”

Design, Synthesis, and Biological Effect Studies of Novel Benzofuran–Thiazolylhydrazone Derivatives as Monoamine Oxidase Inhibitors

“…In addition, it was observed that the compound containing benzofuran, one of the thiosemicarbazone derivatives synthesized by using benzofuran–benzothiophene rings, was more active. Therefore, in this study, new hybrid molecules were obtained by using benzofuran and thiazolylhydrazone pharmacophores. ,,,− …”