Relationship between structure and P-glycoprotein inhibitory activity of dimeric peptides related to the Dmt-Tic pharmacophore

被引：3

作者：

Ambo, Akihiro ^{[1
]}

Ohkatsu, Hiromichi ^{[1
]}

Minamizawa, Motoko ^{[1
]}

Watanabe, Hideko ^{[1
]}

Sugawara, Shigeki ^{[1
]}

Nitta, Kazuo ^{[1
]}

Tsuda, Yuko ^{[2
]}

Okada, Yoshio ^{[2
]}

Sasaki, Yusuke ^{[1
]}

机构：

[1] Tohoku Pharmaceut Univ, Aoba Ku, Sendai, Miyagi 9818558, Japan

[2] Kobe Gakuin Univ, Chuo Ku, Kobe, Hyogo 6508586, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2012年 / 22卷 / 06期

关键词：

Dimeric peptide analogs; P-glycoprotein inhibitory activity; Structure-activity relationship; Dmt-Tic pharmacophore; BLOOD-BRAIN-BARRIER; MULTIDRUG-RESISTANCE; D-PENICILLAMINE(2,5) ENKEPHALIN; ANALOGS; ANTINOCICEPTION; TRANSPORTER; BINDING; CANCER; POTENT; DRUGS;

D O I：

10.1016/j.bmcl.2012.01.107

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

To develop novel inhibitors of P-glycoprotein (P-gp), dimeric peptides related to an opioid peptide containing the Dmt-Tic pharmacophore were synthesized and their P-gp inhibitory activities were analyzed. Of the 30 analogs synthesized, N-alpha,N-epsilon-[(CH3)(2)Mle-Tic](2)Lys-NH2 and its D-Lys analog were found to exhibit potent P-gp inhibitory activity, twice that of verapamil, in doxorubicin-resistant K562 cells. Structure-activity studies indicated that the correct hydrophobicity and spacer length between two aromatic rings are important structural elements in this series of analogs for inhibition of P-gp. (C) 2012 Elsevier Ltd. All rights reserved.

引用

页码：2192 / 2194

页数：3

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