Design and Synthesis of Novel Betulin Derivatives Containing Thio-/Semicarbazone Moieties as Apoptotic Inducers through Mitochindria-Related Pathways

Two new series of betulin derivatives with semicarbazone (7a–g) or thiosemicarbazone (8a–g) groups at the C-28 position were synthesized. All compounds were evaluated for their in vitro cytotoxicities in human hepatocellular...

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Autores principales:	Jiafeng Wang, Jiale Wu, Yinglong Han, Jie Zhang, Yu Lin, Haijun Wang, Jing Wang, Jicheng Liu, Ming Bu
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	betulin derivatives thiosemicarbazone semicarbazone antitumor apoptosis Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/089ba256ef8142eab819af0367c6873a
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spelling	oai:doaj.org-article:089ba256ef8142eab819af0367c6873a2021-11-11T18:23:08ZDesign and Synthesis of Novel Betulin Derivatives Containing Thio-/Semicarbazone Moieties as Apoptotic Inducers through Mitochindria-Related Pathways10.3390/molecules262163561420-3049https://doaj.org/article/089ba256ef8142eab819af0367c6873a2021-10-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6356https://doaj.org/toc/1420-3049Two new series of betulin derivatives with semicarbazone (<b>7a</b>–<b>g</b>) or thiosemicarbazone (<b>8a</b>–<b>g</b>) groups at the C-28 position were synthesized. All compounds were evaluated for their in vitro cytotoxicities in human hepatocellular carcinoma cells (HepG2), human breast carcinoma cells (MCF-7), human lung carcinoma cells (A549), human colorectal cells (HCT-116) and normal human gastric epithelial cells (GES-1). Among these compounds, <b>8f</b> displayed the most potent cytotoxicity with an IC<sub>50</sub> value of 5.86 ± 0.61 μM against MCF-7 cells. Furthermore, the preliminary mechanism studies in MCF-7 cells showed that compound <b>8f</b> could trigger the intracellular mitochondrial-mediated apoptosis pathway by losing MMP level, which was related with the upregulation of Bax, P53 and cytochrome c expression; the downregulation of Bcl-2 expression; activation of the expression levels of caspase-3, caspase-9, cleaved caspase-3 and cleaved caspase-9; and an increase in the amounts of intracellular reactive oxygen species. These results indicated that compound <b>8f</b> may be used as a valuable skeleton structure for developing novel antitumor agents.Jiafeng WangJiale WuYinglong HanJie ZhangYu LinHaijun WangJing WangJicheng LiuMing BuMDPI AGarticlebetulin derivativesthiosemicarbazonesemicarbazoneantitumorapoptosisOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6356, p 6356 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	betulin derivatives thiosemicarbazone semicarbazone antitumor apoptosis Organic chemistry QD241-441
spellingShingle	betulin derivatives thiosemicarbazone semicarbazone antitumor apoptosis Organic chemistry QD241-441 Jiafeng Wang Jiale Wu Yinglong Han Jie Zhang Yu Lin Haijun Wang Jing Wang Jicheng Liu Ming Bu Design and Synthesis of Novel Betulin Derivatives Containing Thio-/Semicarbazone Moieties as Apoptotic Inducers through Mitochindria-Related Pathways
description	Two new series of betulin derivatives with semicarbazone (<b>7a</b>–<b>g</b>) or thiosemicarbazone (<b>8a</b>–<b>g</b>) groups at the C-28 position were synthesized. All compounds were evaluated for their in vitro cytotoxicities in human hepatocellular carcinoma cells (HepG2), human breast carcinoma cells (MCF-7), human lung carcinoma cells (A549), human colorectal cells (HCT-116) and normal human gastric epithelial cells (GES-1). Among these compounds, <b>8f</b> displayed the most potent cytotoxicity with an IC<sub>50</sub> value of 5.86 ± 0.61 μM against MCF-7 cells. Furthermore, the preliminary mechanism studies in MCF-7 cells showed that compound <b>8f</b> could trigger the intracellular mitochondrial-mediated apoptosis pathway by losing MMP level, which was related with the upregulation of Bax, P53 and cytochrome c expression; the downregulation of Bcl-2 expression; activation of the expression levels of caspase-3, caspase-9, cleaved caspase-3 and cleaved caspase-9; and an increase in the amounts of intracellular reactive oxygen species. These results indicated that compound <b>8f</b> may be used as a valuable skeleton structure for developing novel antitumor agents.
format	article
author	Jiafeng Wang Jiale Wu Yinglong Han Jie Zhang Yu Lin Haijun Wang Jing Wang Jicheng Liu Ming Bu
author_facet	Jiafeng Wang Jiale Wu Yinglong Han Jie Zhang Yu Lin Haijun Wang Jing Wang Jicheng Liu Ming Bu
author_sort	Jiafeng Wang
title	Design and Synthesis of Novel Betulin Derivatives Containing Thio-/Semicarbazone Moieties as Apoptotic Inducers through Mitochindria-Related Pathways
title_short	Design and Synthesis of Novel Betulin Derivatives Containing Thio-/Semicarbazone Moieties as Apoptotic Inducers through Mitochindria-Related Pathways
title_full	Design and Synthesis of Novel Betulin Derivatives Containing Thio-/Semicarbazone Moieties as Apoptotic Inducers through Mitochindria-Related Pathways
title_fullStr	Design and Synthesis of Novel Betulin Derivatives Containing Thio-/Semicarbazone Moieties as Apoptotic Inducers through Mitochindria-Related Pathways
title_full_unstemmed	Design and Synthesis of Novel Betulin Derivatives Containing Thio-/Semicarbazone Moieties as Apoptotic Inducers through Mitochindria-Related Pathways
title_sort	design and synthesis of novel betulin derivatives containing thio-/semicarbazone moieties as apoptotic inducers through mitochindria-related pathways
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/089ba256ef8142eab819af0367c6873a
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Design and Synthesis of Novel Betulin Derivatives Containing Thio-/Semicarbazone Moieties as Apoptotic Inducers through Mitochindria-Related Pathways

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