Combretastatin A4-β-Galactosyl Conjugates for Ovarian Cancer Prodrug Monotherapy

被引：29

作者：

Doura, Tomohiro ^{[1
]}

Takahashi, Kazuaki ^{[1
]}

Ogra, Yasumitsu ^{[1
]}

Suzuki, Noriyuki ^{[1
]}

机构：

[1] Chiba Univ, Grad Sch Pharmaceut Sci, Chuo Ku, 1-8-1 Inohana, Chiba 2608675, Japan

来源：

ACS MEDICINAL CHEMISTRY LETTERS | 2017年 / 8卷 / 02期

关键词：

Antitumor agent; prodrug monotherapy; ovarian cancer; tubulin polymerization inhibitor; beta-galactosidase; combretastatin A4; BETA-GALACTOSIDASE; PLASMIN; ANALOGS; POTENT; TUMORS;

D O I：

10.1021/acsmedchemlett.6b00427

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Chemotherapy for ovarian cancer often causes severe side effects. As candidates for combretastatin A4 (CA4) prodrug for ovarian cancer prodrug monotherapy (PMT), we designed and synthesized two beta-galactose-conjugated CA4s (CA4-beta Gals), CA4-beta Gal-1 and CA4-beta Gal-2. CA4 was liberated from CA4-beta Gals by beta-galactosidase, an enzyme more strongly expressed in ovarian cancer cells than normal cells. CA4-beta Gal-2, which has a self-immolative benzyl linker between CA4 and the beta-galactose moiety, was more cytotoxic to ovarian cancer cell lines than CA4-beta Gal-1 without a linker. Therefore, CA4-beta Gal-2 can serve as a platform for the design and manufacture of prodrugs for ovarian cancer PMT.

引用

页码：211 / 214

页数：4

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