Novel nitric oxide-releasing isochroman-4-one derivatives: Synthesis and evaluation of antihypertensive activity

Renren Bai; Xue Yang; Yao Zhu; Zhiwen Zhou; Weijia Xie; Hequan Yao; Jieyun Jiang; Jie Liu; Mingqin Shen; Xiaoming Wu; Jinyi Xu

doi:10.1016/j.bmc.2012.09.043

Novel nitric oxide-releasing isochroman-4-one derivatives: Synthesis and evaluation of antihypertensive activity

Renren Bai, Xue Yang, Yao Zhu, Zhiwen Zhou, Weijia Xie, Hequan Yao, Jieyun Jiang, Jie Liu, Mingqin Shen, Xiaoming Wu, Jinyi Xu

Microbiology, Immunology, and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

Abstract

By coupling nitric oxide (NO)-donor moieties with a natural antihypertensive product (±)-7,8-dihydroxy-3-methyl-isochroman-4-one [(±)-XJP] and its analogue (±)-XJP-B, a series of novel NO-releasing isochroman-4-one derivatives were designed and synthesized. The NO-releasing assay indicated that compounds Ia, Id, IIIb and IIIe released the maximum amount of NO. The maximum reductions of blood pressure of Ia, IIIb and IIIe in SHRs were nearly 40%, which was obviously superior to that of the lead compounds and comparable to that of reference drug captopril. These results suggested that NO-donor/natural product hybrids may provide a promising approach for the discovery of novel antihypertensive agents.

Original language	English
Pages (from-to)	6848-6855
Number of pages	8
Journal	Bioorganic and Medicinal Chemistry
Volume	20
Issue number	23
DOIs	https://doi.org/10.1016/j.bmc.2012.09.043
State	Published - Dec 1 2012

Bibliographical note

Funding Information:
This study was financially supported by a grant from ‘Eleventh Five-Year’ Major Innovation Projects for New Drug Candidates (No. 2009ZX09103-128), Project for Research and Innovation of Graduates in Colleges and Universities of Jiangsu Province (CXZZ11-0798), Fundamental Research Funds for the Central Universities (JKY2011027) and Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University (JKGQ201115).

Keywords

Antihypertensive activity
Hybrids
Isochroman-4-one derivatives
Nitric oxide (NO)
Structure modification

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmc.2012.09.043

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title = "Novel nitric oxide-releasing isochroman-4-one derivatives: Synthesis and evaluation of antihypertensive activity",

abstract = "By coupling nitric oxide (NO)-donor moieties with a natural antihypertensive product (±)-7,8-dihydroxy-3-methyl-isochroman-4-one [(±)-XJP] and its analogue (±)-XJP-B, a series of novel NO-releasing isochroman-4-one derivatives were designed and synthesized. The NO-releasing assay indicated that compounds Ia, Id, IIIb and IIIe released the maximum amount of NO. The maximum reductions of blood pressure of Ia, IIIb and IIIe in SHRs were nearly 40%, which was obviously superior to that of the lead compounds and comparable to that of reference drug captopril. These results suggested that NO-donor/natural product hybrids may provide a promising approach for the discovery of novel antihypertensive agents.",

keywords = "Antihypertensive activity, Hybrids, Isochroman-4-one derivatives, Nitric oxide (NO), Structure modification",

author = "Renren Bai and Xue Yang and Yao Zhu and Zhiwen Zhou and Weijia Xie and Hequan Yao and Jieyun Jiang and Jie Liu and Mingqin Shen and Xiaoming Wu and Jinyi Xu",

note = "Funding Information: This study was financially supported by a grant from {\textquoteleft}Eleventh Five-Year{\textquoteright} Major Innovation Projects for New Drug Candidates (No. 2009ZX09103-128), Project for Research and Innovation of Graduates in Colleges and Universities of Jiangsu Province (CXZZ11-0798), Fundamental Research Funds for the Central Universities (JKY2011027) and Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University (JKGQ201115). ",

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doi = "10.1016/j.bmc.2012.09.043",

language = "English",

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TY - JOUR

T1 - Novel nitric oxide-releasing isochroman-4-one derivatives

T2 - Synthesis and evaluation of antihypertensive activity

AU - Bai, Renren

AU - Yang, Xue

AU - Zhu, Yao

AU - Zhou, Zhiwen

AU - Xie, Weijia

AU - Yao, Hequan

AU - Jiang, Jieyun

AU - Liu, Jie

AU - Shen, Mingqin

AU - Wu, Xiaoming

AU - Xu, Jinyi

N1 - Funding Information: This study was financially supported by a grant from ‘Eleventh Five-Year’ Major Innovation Projects for New Drug Candidates (No. 2009ZX09103-128), Project for Research and Innovation of Graduates in Colleges and Universities of Jiangsu Province (CXZZ11-0798), Fundamental Research Funds for the Central Universities (JKY2011027) and Project Program of State Key Laboratory of Natural Medicines, China Pharmaceutical University (JKGQ201115).

PY - 2012/12/1

Y1 - 2012/12/1

N2 - By coupling nitric oxide (NO)-donor moieties with a natural antihypertensive product (±)-7,8-dihydroxy-3-methyl-isochroman-4-one [(±)-XJP] and its analogue (±)-XJP-B, a series of novel NO-releasing isochroman-4-one derivatives were designed and synthesized. The NO-releasing assay indicated that compounds Ia, Id, IIIb and IIIe released the maximum amount of NO. The maximum reductions of blood pressure of Ia, IIIb and IIIe in SHRs were nearly 40%, which was obviously superior to that of the lead compounds and comparable to that of reference drug captopril. These results suggested that NO-donor/natural product hybrids may provide a promising approach for the discovery of novel antihypertensive agents.

AB - By coupling nitric oxide (NO)-donor moieties with a natural antihypertensive product (±)-7,8-dihydroxy-3-methyl-isochroman-4-one [(±)-XJP] and its analogue (±)-XJP-B, a series of novel NO-releasing isochroman-4-one derivatives were designed and synthesized. The NO-releasing assay indicated that compounds Ia, Id, IIIb and IIIe released the maximum amount of NO. The maximum reductions of blood pressure of Ia, IIIb and IIIe in SHRs were nearly 40%, which was obviously superior to that of the lead compounds and comparable to that of reference drug captopril. These results suggested that NO-donor/natural product hybrids may provide a promising approach for the discovery of novel antihypertensive agents.

KW - Antihypertensive activity

KW - Hybrids

KW - Isochroman-4-one derivatives

KW - Nitric oxide (NO)

KW - Structure modification

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Novel nitric oxide-releasing isochroman-4-one derivatives: Synthesis and evaluation of antihypertensive activity

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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