Design and Synthesis of 3-Carbamoylbenzoic Acid Derivatives as Inhibitors of Human Apurinic/Apyrimidinic Endonuclease 1 (APE1)

被引：10

作者：

Aiello, Francesca ^{[1
]}

Shabaik, Yumna ^{[2
]}

Esqueda, Adrian ^{[2
]}

Sanchez, Tino W. ^{[2
]}

Grande, Fedora ^{[1
]}

Garofalo, Antonio ^{[1
]}

Neamati, Nouri ^{[2
]}

机构：

[1] Univ Calabria, Dipartimento Sci Farmaceut, I-87036 Arcavacata Di Rende, CS, Italy

[2] Univ So Calif, Sch Pharm, Dept Pharmacol & Pharmaceut Sci, Los Angeles, CA 90089 USA

来源：

CHEMMEDCHEM | 2012年 / 7卷 / 10期

关键词：

anticancer agents; APE1; carbamoylbenzoic acids; inhibitors; synthesis; DNA-REPAIR ENZYME; PROGNOSTIC-SIGNIFICANCE; SUBCELLULAR-LOCALIZATION; OVARIAN-CANCER; BASE EXCISION; APE1/REF-1; EXPRESSION; BINDING; CELL; RNA;

D O I：

10.1002/cmdc.201200334

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Apurinic/apyrimidinic (AP) endonuclease 1 (APE1) is a multifaceted protein with an essential role in the base excision repair (BER) pathway. Its implication in tumor development, progression, and resistance has been confirmed in multiple cancers, making it a viable target for intensive investigation. In this work, we designed and synthesized different classes of small-molecule inhibitors of the catalytic endonuclease function of APE1 that contain a 3-carbamoylbenzoic acid scaffold. Further structural modifications were made with the aim of increasing the activity and cytotoxicity of these inhibitors. Several of our compounds were shown to inhibit the catalytic endonuclease function of APE1 with potencies in the low-micromolar range in vitro, and therefore represent novel classes of APE1 inhibitors worthy of further development.

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收藏

页码：1825 / 1839

页数：15

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