Design, synthesis, and evaluation of novel (E)‐N'‐(3‐allyl‐2‐hydroxy)benzylidene‐2‐(4‐oxoquinazolin‐3(4H)‐yl)acetohydrazides as antitumor agents

202100216

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Bibliographic Details
Main Authors: Do T. M. Dung, Eun J. Park, Duong T. Anh, Pham, The Hai, Le D. Huy, Hye W. Jun, Joo-Hee Kwon, A. Young Ji, Jong S. Kang, Truong T. Tung, Phan T. P. Dung, Sang-Bae Han, Nguyen-Hai Nam
Format: Bài báo khoa học
Language:English
Published: Archiv der Pharmazie 2022
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Online Access:https://dlib.phenikaa-uni.edu.vn/handle/PNK/4005
https://doi.org/10.1002/ardp.202100216
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spelling oai:localhost:PNK-40052022-08-17T05:54:47Z Design, synthesis, and evaluation of novel (E)‐N'‐(3‐allyl‐2‐hydroxy)benzylidene‐2‐(4‐oxoquinazolin‐3(4H)‐yl)acetohydrazides as antitumor agents Do T. M. Dung Eun J. Park Duong T. Anh Pham, The Hai Le D. Huy Hye W. Jun Joo-Hee Kwon A. Young Ji Jong S. Kang Truong T. Tung Phan T. P. Dung Sang-Bae Han Nguyen-Hai Nam Acetohydrazides caspase activation 202100216 In our continuing search for novel small‐molecule anticancer agents, we designedand synthesized a series of novel (E)‐N'‐(3‐allyl‐2‐hydroxy)benzylidene‐2‐(4‐oxoquinazolin‐3(4H)‐yl)acetohydrazides (5), focusing on the modification of sub-stitution in the quinazolin‐4(3H)‐one moiety. The biological evaluation showed thatall 13 designed and synthesized compounds displayed significant cytotoxicity againstthree human cancer cell lines (SW620, colon cancer; PC‐3, prostate cancer; NCI‐H23, lung cancer). The most potent compound5ldisplayed cytotoxicity up to 213‐fold more potent than 5‐fluorouracil and 87‐fold more potent than PAC‐1, the firstprocaspase‐activating compound. Structure–activity relationship analysis revealedthat substitution of either electron‐withdrawing or electron‐releasing groups atpositions 6 or 7 on the quinazolin‐4(3H)‐4‐one moiety increased the cytotoxicity ofthe compounds, but substitution at position 6 seemed to be more favorable. In thecaspase activation assay, compound5lwas found to activate the caspase activity by291% in comparison to PAC‐1, which was used as a control. Further docking si-mulation also revealed that this compound may be a potent allosteric inhibitor ofprocaspase‐3 through chelation of the inhibitory zinc ion. Physicochemical andADMET calculations for5lprovided useful information of its suitable absorptionprofile and some toxicological effects that need further optimization to be devel-oped as a promising anticancer agent 2022-01-17T02:27:17Z 2022-01-17T02:27:17Z 2021 Bài báo khoa học https://dlib.phenikaa-uni.edu.vn/handle/PNK/4005 https://doi.org/10.1002/ardp.202100216 en Archiv der Pharmazie
institution Digital Phenikaa
collection Digital Phenikaa
language English
topic Acetohydrazides
caspase activation
spellingShingle Acetohydrazides
caspase activation
Do T. M. Dung
Eun J. Park
Duong T. Anh
Pham, The Hai
Le D. Huy
Hye W. Jun
Joo-Hee Kwon
A. Young Ji
Jong S. Kang
Truong T. Tung
Phan T. P. Dung
Sang-Bae Han
Nguyen-Hai Nam
Design, synthesis, and evaluation of novel (E)‐N'‐(3‐allyl‐2‐hydroxy)benzylidene‐2‐(4‐oxoquinazolin‐3(4H)‐yl)acetohydrazides as antitumor agents
description 202100216
format Bài báo khoa học
author Do T. M. Dung
Eun J. Park
Duong T. Anh
Pham, The Hai
Le D. Huy
Hye W. Jun
Joo-Hee Kwon
A. Young Ji
Jong S. Kang
Truong T. Tung
Phan T. P. Dung
Sang-Bae Han
Nguyen-Hai Nam
author_facet Do T. M. Dung
Eun J. Park
Duong T. Anh
Pham, The Hai
Le D. Huy
Hye W. Jun
Joo-Hee Kwon
A. Young Ji
Jong S. Kang
Truong T. Tung
Phan T. P. Dung
Sang-Bae Han
Nguyen-Hai Nam
author_sort Do T. M. Dung
title Design, synthesis, and evaluation of novel (E)‐N'‐(3‐allyl‐2‐hydroxy)benzylidene‐2‐(4‐oxoquinazolin‐3(4H)‐yl)acetohydrazides as antitumor agents
title_short Design, synthesis, and evaluation of novel (E)‐N'‐(3‐allyl‐2‐hydroxy)benzylidene‐2‐(4‐oxoquinazolin‐3(4H)‐yl)acetohydrazides as antitumor agents
title_full Design, synthesis, and evaluation of novel (E)‐N'‐(3‐allyl‐2‐hydroxy)benzylidene‐2‐(4‐oxoquinazolin‐3(4H)‐yl)acetohydrazides as antitumor agents
title_fullStr Design, synthesis, and evaluation of novel (E)‐N'‐(3‐allyl‐2‐hydroxy)benzylidene‐2‐(4‐oxoquinazolin‐3(4H)‐yl)acetohydrazides as antitumor agents
title_full_unstemmed Design, synthesis, and evaluation of novel (E)‐N'‐(3‐allyl‐2‐hydroxy)benzylidene‐2‐(4‐oxoquinazolin‐3(4H)‐yl)acetohydrazides as antitumor agents
title_sort design, synthesis, and evaluation of novel (e)‐n'‐(3‐allyl‐2‐hydroxy)benzylidene‐2‐(4‐oxoquinazolin‐3(4h)‐yl)acetohydrazides as antitumor agents
publisher Archiv der Pharmazie
publishDate 2022
url https://dlib.phenikaa-uni.edu.vn/handle/PNK/4005
https://doi.org/10.1002/ardp.202100216
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