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^*

^*この論文の責任著者

薬品製造学研究室

研究成果: ジャーナルへの寄稿 › 学術論文 › 査読

16 被引用数 (Scopus)

抄録

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.

本文言語	英語
ページ（範囲）	4383-4388
ページ数	6
ジャーナル	Bioorganic and Medicinal Chemistry
巻	13
号	14
DOI	https://doi.org/10.1016/j.bmc.2005.04.056
出版ステータス	出版済み - 2005/07/15

ASJC Scopus 主題領域

生化学
分子医療
分子生物学
薬科学
創薬
臨床生化学
有機化学

文献へのアクセス

10.1016/j.bmc.2005.04.056

引用スタイル

@article{0808fafb51f0468ab5387ecd5916538b,

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",

month = jul,

day = "15",

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

language = "英語",

volume = "13",

pages = "4383--4388",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Ltd.",

number = "14",

}

TY - JOUR

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

UR - http://www.scopus.com/inward/record.url?scp=20444455845&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2005.04.056

DO - 10.1016/j.bmc.2005.04.056

M3 - 学術論文

C2 - 15908223

AN - SCOPUS:20444455845

SN - 0968-0896

VL - 13

SP - 4383

EP - 4388

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

IS - 14

ER -

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

抄録

ASJC Scopus 主題領域

文献へのアクセス

フィンガープリント

引用スタイル