Gobbi Silvia, Cavalli Andrea, Bisi Alessandra, Recanatini Maurizio
Department of Pharmaceutical Sciences, University of Bologna, Via Belmeloro, 6, I-40126 Bologna, Italy.
Curr Top Med Chem. 2008;8(10):869-87. doi: 10.2174/156802608784911590.
Aromatase is the enzyme responsible for the conversion of androgens to estrogens and represents the main source of local estrogens in post-menopausal breast cancer tissue. Nonsteroidal aromatase inhibitors (NSAIs) are able to reduce growth-stimulatory effects of estrogens in hormone-dependent breast cancer, and third generation NSAIs are currently approved as first-line therapy for the treatment of postmenopausal women with metastatic advanced breast cancer. Nevertheless, some issues in this area still need to be addressed and research efforts are aimed both at identifying new molecules of therapeutic interest and at exploring different options for the modulation of this enzyme. In this review, an update of the latest developments in the field of NSAIs is presented, to provide a broad view on the recent progress in this area. Beside classical structure-activity relationships studies and development of natural product derivatives, rational approaches for both ligand- and structure-based design are described. Moreover, novel strategies for the development of multitarget-directed molecules are also presented. Finally, some possible future developments in this research area are briefly considered.
芳香化酶是负责将雄激素转化为雌激素的酶，是绝经后乳腺癌组织中局部雌激素的主要来源。非甾体类芳香化酶抑制剂（NSAIs）能够降低雌激素对激素依赖性乳腺癌的生长刺激作用，第三代NSAIs目前已被批准作为治疗绝经后转移性晚期乳腺癌女性的一线疗法。然而，该领域的一些问题仍有待解决，研究工作旨在识别具有治疗意义的新分子，并探索调节这种酶的不同方法。在这篇综述中，介绍了NSAIs领域的最新进展，以提供该领域近期进展的全面观点。除了经典的构效关系研究和天然产物衍生物的开发外，还描述了基于配体和基于结构的设计的合理方法。此外，还介绍了开发多靶点导向分子的新策略。最后，简要考虑了该研究领域未来可能的一些发展。
