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

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 derivati...

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Autores principales:	Derya Osmaniye, Berkant Kurban, Begüm Nurpelin Sağlık, Serkan Levent, Yusuf Özkay, Zafer Asım Kaplancıklı
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	thiosemicarbazone benzofuran benzothiophene <i>h</i>MAO enzymes molecular docking Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/cfe17d4976e34513ab429bd9d92e62c3
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spelling	oai:doaj.org-article:cfe17d4976e34513ab429bd9d92e62c32021-11-11T18:36:52ZNovel Thiosemicarbazone Derivatives: In Vitro and In Silico Evaluation as Potential MAO-B Inhibitors10.3390/molecules262166401420-3049https://doaj.org/article/cfe17d4976e34513ab429bd9d92e62c32021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6640https://doaj.org/toc/1420-3049MAO-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 <i>h</i>MAO 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 <i>h</i>MAO-A and <i>h</i>MAO-B inhibitory activity by an in vitro fluorometric method. The compounds including methoxyethyl substituent (<b>2b</b> and <b>2h</b>) were found to be the most effective agents in the series against MAO-B enzyme with the IC<sub>50</sub> value of 0.042 ± 0.002 µM and 0.056 ± 0.002 µM, respectively. The mechanism of <i>h</i>MAO-B inhibition of compounds <b>2b</b> and <b>2h</b> was investigated by Lineweaver–Burk graphics. Compounds <b>2b</b> and <b>2h</b> were reversible and non-competitive inhibitors with similar inhibition features as the substrates. The K<sub>i</sub> values of compounds <b>2b</b> and <b>2h</b> were calculated as 0.035 µM and 0.046 µM, respectively, with the help of secondary plots. The docking study of compound <b>2b</b> and <b>2h</b> revealed that there is a strong interaction between the active sites of <i>h</i>MAO-B and analyzed compound.Derya OsmaniyeBerkant KurbanBegüm Nurpelin SağlıkSerkan LeventYusuf ÖzkayZafer Asım KaplancıklıMDPI AGarticlethiosemicarbazonebenzofuranbenzothiophene<i>h</i>MAO enzymesmolecular dockingOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6640, p 6640 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	thiosemicarbazone benzofuran benzothiophene <i>h</i>MAO enzymes molecular docking Organic chemistry QD241-441
spellingShingle	thiosemicarbazone benzofuran benzothiophene <i>h</i>MAO enzymes molecular docking Organic chemistry QD241-441 Derya Osmaniye Berkant Kurban Begüm Nurpelin Sağlık Serkan Levent Yusuf Özkay Zafer Asım Kaplancıklı Novel Thiosemicarbazone Derivatives: In Vitro and In Silico Evaluation as Potential MAO-B Inhibitors
description	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 <i>h</i>MAO 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 <i>h</i>MAO-A and <i>h</i>MAO-B inhibitory activity by an in vitro fluorometric method. The compounds including methoxyethyl substituent (<b>2b</b> and <b>2h</b>) were found to be the most effective agents in the series against MAO-B enzyme with the IC<sub>50</sub> value of 0.042 ± 0.002 µM and 0.056 ± 0.002 µM, respectively. The mechanism of <i>h</i>MAO-B inhibition of compounds <b>2b</b> and <b>2h</b> was investigated by Lineweaver–Burk graphics. Compounds <b>2b</b> and <b>2h</b> were reversible and non-competitive inhibitors with similar inhibition features as the substrates. The K<sub>i</sub> values of compounds <b>2b</b> and <b>2h</b> were calculated as 0.035 µM and 0.046 µM, respectively, with the help of secondary plots. The docking study of compound <b>2b</b> and <b>2h</b> revealed that there is a strong interaction between the active sites of <i>h</i>MAO-B and analyzed compound.
format	article
author	Derya Osmaniye Berkant Kurban Begüm Nurpelin Sağlık Serkan Levent Yusuf Özkay Zafer Asım Kaplancıklı
author_facet	Derya Osmaniye Berkant Kurban Begüm Nurpelin Sağlık Serkan Levent Yusuf Özkay Zafer Asım Kaplancıklı
author_sort	Derya Osmaniye
title	Novel Thiosemicarbazone Derivatives: In Vitro and In Silico Evaluation as Potential MAO-B Inhibitors
title_short	Novel Thiosemicarbazone Derivatives: In Vitro and In Silico Evaluation as Potential MAO-B Inhibitors
title_full	Novel Thiosemicarbazone Derivatives: In Vitro and In Silico Evaluation as Potential MAO-B Inhibitors
title_fullStr	Novel Thiosemicarbazone Derivatives: In Vitro and In Silico Evaluation as Potential MAO-B Inhibitors
title_full_unstemmed	Novel Thiosemicarbazone Derivatives: In Vitro and In Silico Evaluation as Potential MAO-B Inhibitors
title_sort	novel thiosemicarbazone derivatives: in vitro and in silico evaluation as potential mao-b inhibitors
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/cfe17d4976e34513ab429bd9d92e62c3
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Novel Thiosemicarbazone Derivatives: In Vitro and In Silico Evaluation as Potential MAO-B Inhibitors

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