Effects of the aryl linker and the aromatic substituent on the anti-HCV activities of aryl diketoacid (ADK) analogues

Jinyoung Kim; Ki Sun Kim; Hyo Seon Lee; Kwang Su Park; Sun Young Park; Seock Yong Kang; Soo Jae Lee; Hyung Soon Park; Dong Eun Kim; Youhoon Chong

doi:10.1016/j.bmcl.2008.07.008

Effects of the aryl linker and the aromatic substituent on the anti-HCV activities of aryl diketoacid (ADK) analogues

Jinyoung Kim, Ki Sun Kim, Hyo Seon Lee, Kwang Su Park, Sun Young Park, Seock Yong Kang, Soo Jae Lee, Hyung Soon Park, Dong Eun Kim, Youhoon Chong

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

19 Scopus citations

Abstract

Based on our pharmacophore model of the aryl diketoacids (ADKs), we designed and prepared a series of novel ADK analogues, which showed potent inhibitory activities against the NS5B polymerase in the submicromolar range. Pharmacophore-guided docking study revealed that the antiviral activities of the ADKs are highly dependent upon the aryl linker as well as the size and position of the aromatic substituent. It is of another importance that, unlike previously reported ADKs, three ADK analogues synthesized in this study effectively blocked Hepatitis C Virus (HCV) replication in the replicon systems.

Original language	English
Pages (from-to)	4661-4665
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	16
DOIs	https://doi.org/10.1016/j.bmcl.2008.07.008
State	Published - 15 Aug 2008
Externally published	Yes

Keywords

Aromatic substituent
Aryl diketoacid (ADK)
Aryl linker
Hepatitis C virus (HCV)
Pharmacophore-guided docking

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10.1016/j.bmcl.2008.07.008

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@article{83c61023b0d741cf854ee19a7007320b,

title = "Effects of the aryl linker and the aromatic substituent on the anti-HCV activities of aryl diketoacid (ADK) analogues",

abstract = "Based on our pharmacophore model of the aryl diketoacids (ADKs), we designed and prepared a series of novel ADK analogues, which showed potent inhibitory activities against the NS5B polymerase in the submicromolar range. Pharmacophore-guided docking study revealed that the antiviral activities of the ADKs are highly dependent upon the aryl linker as well as the size and position of the aromatic substituent. It is of another importance that, unlike previously reported ADKs, three ADK analogues synthesized in this study effectively blocked Hepatitis C Virus (HCV) replication in the replicon systems.",

keywords = "Aromatic substituent, Aryl diketoacid (ADK), Aryl linker, Hepatitis C virus (HCV), Pharmacophore-guided docking",

author = "Jinyoung Kim and Kim, \{Ki Sun\} and Lee, \{Hyo Seon\} and Park, \{Kwang Su\} and Park, \{Sun Young\} and Kang, \{Seock Yong\} and Lee, \{Soo Jae\} and Park, \{Hyung Soon\} and Kim, \{Dong Eun\} and Youhoon Chong",

note = "Funding Information: This work was supported by Grant No. KRF-2007-313-C00476 from the Korea Research Foundation, Republic of Korea (MOEHRD, Basic Research Promotion Fund) and by grants from Biogreen 21 (Korea Ministry of Agriculture and Forestry), and the second Brain Korea 21 (Korea Ministry of Education). J.K. and H.S.L. are supported by the second Brain Korea 21.",

year = "2008",

month = aug,

day = "15",

doi = "10.1016/j.bmcl.2008.07.008",

language = "English",

volume = "18",

pages = "4661--4665",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Ltd.",

number = "16",

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TY - JOUR

T1 - Effects of the aryl linker and the aromatic substituent on the anti-HCV activities of aryl diketoacid (ADK) analogues

AU - Kim, Jinyoung

AU - Kim, Ki Sun

AU - Lee, Hyo Seon

AU - Park, Kwang Su

AU - Park, Sun Young

AU - Kang, Seock Yong

AU - Lee, Soo Jae

AU - Park, Hyung Soon

AU - Kim, Dong Eun

AU - Chong, Youhoon

N1 - Funding Information: This work was supported by Grant No. KRF-2007-313-C00476 from the Korea Research Foundation, Republic of Korea (MOEHRD, Basic Research Promotion Fund) and by grants from Biogreen 21 (Korea Ministry of Agriculture and Forestry), and the second Brain Korea 21 (Korea Ministry of Education). J.K. and H.S.L. are supported by the second Brain Korea 21.

PY - 2008/8/15

Y1 - 2008/8/15

N2 - Based on our pharmacophore model of the aryl diketoacids (ADKs), we designed and prepared a series of novel ADK analogues, which showed potent inhibitory activities against the NS5B polymerase in the submicromolar range. Pharmacophore-guided docking study revealed that the antiviral activities of the ADKs are highly dependent upon the aryl linker as well as the size and position of the aromatic substituent. It is of another importance that, unlike previously reported ADKs, three ADK analogues synthesized in this study effectively blocked Hepatitis C Virus (HCV) replication in the replicon systems.

AB - Based on our pharmacophore model of the aryl diketoacids (ADKs), we designed and prepared a series of novel ADK analogues, which showed potent inhibitory activities against the NS5B polymerase in the submicromolar range. Pharmacophore-guided docking study revealed that the antiviral activities of the ADKs are highly dependent upon the aryl linker as well as the size and position of the aromatic substituent. It is of another importance that, unlike previously reported ADKs, three ADK analogues synthesized in this study effectively blocked Hepatitis C Virus (HCV) replication in the replicon systems.

KW - Aromatic substituent

KW - Aryl diketoacid (ADK)

KW - Aryl linker

KW - Hepatitis C virus (HCV)

KW - Pharmacophore-guided docking

UR - https://www.scopus.com/pages/publications/48649084902

U2 - 10.1016/j.bmcl.2008.07.008

DO - 10.1016/j.bmcl.2008.07.008

M3 - Article

C2 - 18644717

AN - SCOPUS:48649084902

SN - 0960-894X

VL - 18

SP - 4661

EP - 4665

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 16

ER -

Effects of the aryl linker and the aromatic substituent on the anti-HCV activities of aryl diketoacid (ADK) analogues

Abstract

Keywords

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