Doura Tomohiro, Takahashi Kazuaki, Ogra Yasumitsu, Suzuki Noriyuki
Graduate School of Pharmaceutical Sciences, Chiba University , 1-8-1 Inohana, Chuo-ku, Chiba 260-8675, Japan.
ACS Med Chem Lett. 2017 Jan 20;8(2):211-214. doi: 10.1021/acsmedchemlett.6b00427. eCollection 2017 Feb 9.
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 β-galactose-conjugated CA4s (CA4-βGals), CA4-βGal-1 and CA4-βGal-2. CA4 was liberated from CA4-βGals by β-galactosidase, an enzyme more strongly expressed in ovarian cancer cells than normal cells. CA4-βGal-2, which has a self-immolative benzyl linker between CA4 and the β-galactose moiety, was more cytotoxic to ovarian cancer cell lines than CA4-βGal-1 without a linker. Therefore, CA4-βGal-2 can serve as a platform for the design and manufacture of prodrugs for ovarian cancer PMT.
卵巢癌化疗常常会引发严重的副作用。作为卵巢癌前药单一疗法（PMT）中康普瑞汀A4（CA4）前药的候选药物，我们设计并合成了两种β-半乳糖共轭CA4（CA4-βGal），即CA4-βGal-1和CA4-βGal-2。CA4可通过β-半乳糖苷酶从CA4-βGal中释放出来，该酶在卵巢癌细胞中的表达比正常细胞更强。在CA4和β-半乳糖部分之间具有自毁型苄基连接子的CA4-βGal-2，对卵巢癌细胞系的细胞毒性比没有连接子的CA4-βGal-1更强。因此，CA4-βGal-2可作为设计和制造用于卵巢癌PMT前药的一个平台。
