Synthesis of new phorbol derivatives having ethereal side chain and evaluation of their anti-HIV activity

Yuji Matsuya; Zhong Yu; Naoki Yamamoto; Masao Mori; Haruo Saito; Makoto Takeuchi; Mamiko Ito; Hideo Nemoto

doi:10.1016/j.bmc.2005.04.056

Synthesis of new phorbol derivatives having ethereal side chain and evaluation of their anti-HIV activity

Yuji Matsuya, Zhong Yu, Naoki Yamamoto, Masao Mori, Haruo Saito, Makoto Takeuchi, Mamiko Ito, Hideo Nemoto^*

^*Corresponding author for this work

Synthetic and Medicinal Chemistry

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

16 Scopus citations

Abstract

Several new phorbol derivatives having ethereal substituents at the 12-position were synthesized and subjected to biological evaluation to find new candidates of an anti-HIV agent. Among them, 12-O-(methoxymethyl)phorbol 13-decanoate showed potent inhibitory activity against infection of HIV-1 in MT-4 cells (EC₅₀: 1.3 ng/mL) and relatively low cytotoxicity (CC ₅₀: 8.3 μg/mL). This compound was also found to have sufficient stability in mouse plasma compared with the corresponding 12-acetate derivative, which was an equipotent HIV-1 inhibitor, but with an activity that decreased considerably after plasma treatment.

Original language	English
Pages (from-to)	4383-4388
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry
Volume	13
Issue number	14
DOIs	https://doi.org/10.1016/j.bmc.2005.04.056
State	Published - 2005/07/15

Keywords

Anti-HIV agents
Ethereal side chain
Phorbol
Safety index

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.2005.04.056

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title = "Synthesis of new phorbol derivatives having ethereal side chain and evaluation of their anti-HIV activity",

abstract = "Several new phorbol derivatives having ethereal substituents at the 12-position were synthesized and subjected to biological evaluation to find new candidates of an anti-HIV agent. Among them, 12-O-(methoxymethyl)phorbol 13-decanoate showed potent inhibitory activity against infection of HIV-1 in MT-4 cells (EC50: 1.3 ng/mL) and relatively low cytotoxicity (CC 50: 8.3 μg/mL). This compound was also found to have sufficient stability in mouse plasma compared with the corresponding 12-acetate derivative, which was an equipotent HIV-1 inhibitor, but with an activity that decreased considerably after plasma treatment.",

keywords = "Anti-HIV agents, Ethereal side chain, Phorbol, Safety index",

author = "Yuji Matsuya and Zhong Yu and Naoki Yamamoto and Masao Mori and Haruo Saito and Makoto Takeuchi and Mamiko Ito and Hideo Nemoto",

year = "2005",

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doi = "10.1016/j.bmc.2005.04.056",

language = "英語",

volume = "13",

pages = "4383--4388",

journal = "Bioorganic and Medicinal Chemistry",

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T1 - Synthesis of new phorbol derivatives having ethereal side chain and evaluation of their anti-HIV activity

AU - Matsuya, Yuji

AU - Yu, Zhong

AU - Yamamoto, Naoki

AU - Mori, Masao

AU - Saito, Haruo

AU - Takeuchi, Makoto

AU - Ito, Mamiko

AU - Nemoto, Hideo

PY - 2005/7/15

Y1 - 2005/7/15

N2 - Several new phorbol derivatives having ethereal substituents at the 12-position were synthesized and subjected to biological evaluation to find new candidates of an anti-HIV agent. Among them, 12-O-(methoxymethyl)phorbol 13-decanoate showed potent inhibitory activity against infection of HIV-1 in MT-4 cells (EC50: 1.3 ng/mL) and relatively low cytotoxicity (CC 50: 8.3 μg/mL). This compound was also found to have sufficient stability in mouse plasma compared with the corresponding 12-acetate derivative, which was an equipotent HIV-1 inhibitor, but with an activity that decreased considerably after plasma treatment.

AB - Several new phorbol derivatives having ethereal substituents at the 12-position were synthesized and subjected to biological evaluation to find new candidates of an anti-HIV agent. Among them, 12-O-(methoxymethyl)phorbol 13-decanoate showed potent inhibitory activity against infection of HIV-1 in MT-4 cells (EC50: 1.3 ng/mL) and relatively low cytotoxicity (CC 50: 8.3 μg/mL). This compound was also found to have sufficient stability in mouse plasma compared with the corresponding 12-acetate derivative, which was an equipotent HIV-1 inhibitor, but with an activity that decreased considerably after plasma treatment.

KW - Anti-HIV agents

KW - Ethereal side chain

KW - Phorbol

KW - Safety index

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JF - Bioorganic and Medicinal Chemistry

IS - 14

ER -

Synthesis of new phorbol derivatives having ethereal side chain and evaluation of their anti-HIV activity

Abstract

Keywords

ASJC Scopus subject areas

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