Synthesis and Structure–Activity Relationship of Palmatine Derivatives as a Novel Class of Antibacterial Agents against Helicobacter pylori

Taking palmatine (PMT) as the lead, 20 new PMT derivatives were synthesized and examined for their antibacterial activities against six tested metronidazole (MTZ)-resistant Helicobacter pylori (H. pylori) strains. The structure−activity relationship (S...

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Main Authors:	Tianyun Fan, Xixi Guo, Qingxuan Zeng, Wei Wei, Xuefu You, Jing Pang, Yanxiang Wang, Danqing Song
Format:	Article
Language:	English
Published:	MDPI AG 2020-03-01
Series:	Molecules
Subjects:	<i>helicobacter pylori</i> palmatine synthesis structure–activity relationship urease
Online Access:	https://www.mdpi.com/1420-3049/25/6/1352

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spelling	doaj-2e78980debf84268942fec5c18f38bc22020-11-25T01:37:45ZengMDPI AGMolecules1420-30492020-03-01256135210.3390/molecules25061352molecules25061352Synthesis and Structure–Activity Relationship of Palmatine Derivatives as a Novel Class of Antibacterial Agents against <i>Helicobacter pylori</i>Tianyun Fan0Xixi Guo1Qingxuan Zeng2Wei Wei3Xuefu You4Jing Pang5Yanxiang Wang6Danqing Song7Beijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaBeijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaBeijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaBeijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaBeijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaBeijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaBeijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaBeijing Key Laboratory of Antimicrobial Agents, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaTaking palmatine (PMT) as the lead, 20 new PMT derivatives were synthesized and examined for their antibacterial activities against six tested metronidazole (MTZ)-resistant <i>Helicobacter pylori</i> (<i>H. pylori</i>) strains. The structure−activity relationship (SAR) indicated that the introduction of a suitable secondary amine substituent at the 9-position might be beneficial for potency. Among them, compound <b>1c</b> exhibited the most potent activities against MTZ-resistant strains, with minimum inhibitory concentration (MIC) values of 4−16 μg/mL, better than that of the lead. It also exhibited a good safety profile with a half-lethal dose (LD<sub>50</sub>) of over 1000 mg/kg. Meanwhile, <b>1c</b> might exert its antimicrobial activity through targeting <i>H. pylori</i> urease. These results suggested that PMT derivatives might be a new family of anti-<i>H. pylori</i> components.https://www.mdpi.com/1420-3049/25/6/1352<i>helicobacter pylori</i>palmatinesynthesisstructure–activity relationshipurease
collection	DOAJ
language	English
format	Article
sources	DOAJ
author	Tianyun Fan Xixi Guo Qingxuan Zeng Wei Wei Xuefu You Jing Pang Yanxiang Wang Danqing Song
spellingShingle	Tianyun Fan Xixi Guo Qingxuan Zeng Wei Wei Xuefu You Jing Pang Yanxiang Wang Danqing Song Synthesis and Structure–Activity Relationship of Palmatine Derivatives as a Novel Class of Antibacterial Agents against <i>Helicobacter pylori</i> Molecules <i>helicobacter pylori</i> palmatine synthesis structure–activity relationship urease
author_facet	Tianyun Fan Xixi Guo Qingxuan Zeng Wei Wei Xuefu You Jing Pang Yanxiang Wang Danqing Song
author_sort	Tianyun Fan
title	Synthesis and Structure–Activity Relationship of Palmatine Derivatives as a Novel Class of Antibacterial Agents against <i>Helicobacter pylori</i>
title_short	Synthesis and Structure–Activity Relationship of Palmatine Derivatives as a Novel Class of Antibacterial Agents against <i>Helicobacter pylori</i>
title_full	Synthesis and Structure–Activity Relationship of Palmatine Derivatives as a Novel Class of Antibacterial Agents against <i>Helicobacter pylori</i>
title_fullStr	Synthesis and Structure–Activity Relationship of Palmatine Derivatives as a Novel Class of Antibacterial Agents against <i>Helicobacter pylori</i>
title_full_unstemmed	Synthesis and Structure–Activity Relationship of Palmatine Derivatives as a Novel Class of Antibacterial Agents against <i>Helicobacter pylori</i>
title_sort	synthesis and structure–activity relationship of palmatine derivatives as a novel class of antibacterial agents against <i>helicobacter pylori</i>
publisher	MDPI AG
series	Molecules
issn	1420-3049
publishDate	2020-03-01
description	Taking palmatine (PMT) as the lead, 20 new PMT derivatives were synthesized and examined for their antibacterial activities against six tested metronidazole (MTZ)-resistant <i>Helicobacter pylori</i> (<i>H. pylori</i>) strains. The structure−activity relationship (SAR) indicated that the introduction of a suitable secondary amine substituent at the 9-position might be beneficial for potency. Among them, compound <b>1c</b> exhibited the most potent activities against MTZ-resistant strains, with minimum inhibitory concentration (MIC) values of 4−16 μg/mL, better than that of the lead. It also exhibited a good safety profile with a half-lethal dose (LD<sub>50</sub>) of over 1000 mg/kg. Meanwhile, <b>1c</b> might exert its antimicrobial activity through targeting <i>H. pylori</i> urease. These results suggested that PMT derivatives might be a new family of anti-<i>H. pylori</i> components.
topic	<i>helicobacter pylori</i> palmatine synthesis structure–activity relationship urease
url	https://www.mdpi.com/1420-3049/25/6/1352
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Synthesis and Structure–Activity Relationship of Palmatine Derivatives as a Novel Class of Antibacterial Agents against <i>Helicobacter pylori</i>

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