三阴性乳腺癌是乳腺癌的一种特殊亚型，其恶性程度高、侵袭性强、易远位转移、预后较差。因内分泌与靶向治疗均无效，化学疗法是目前临床上的主要有效疗法。近三年来，我们从泰国、印度红树植物中共分离鉴定了天然萜类新化合物70余个；其中新骨架化合物16个，包括8类共14个新骨架柠檬苦素；发现木果楝属红树植物专有类型柠檬苦素WSC-29对三阴性乳腺癌MDA-MB-453细胞系的裸鼠移植瘤有显著的抑瘤生长作用。本申请项目拟重点以抗三阴性乳腺癌为靶向，结合高效液相色谱、液相-质谱联用、核磁共振波谱、单晶X-射线衍射、圆二色光谱等现代色谱、光谱和波谱技术，从泰国、印度红树植物中挖掘具有靶向抗肿瘤活性的新结构天然柠檬苦素化合物，并经由结构多样性导向化学合成和体内外抗肿瘤活性评价发现抗三阴性乳腺癌新药候选物。

Triple-negative breast cancer is a special subtype of breast cancers. It has a high degree of malignancy, strong invasiveness, easily distant metastasis, and a relatively worse prognosis. Because endocrine and targeted therapies are ineffective, chemotherapy is currently the main effective treatment for triple-negative breast cancer in clinical practice. During recent three years, we have isolated and identified seventy novel natural terpenoids, among which sixteen are new skeletal compounds, including eight classes of limonoids with new frameworks and fourteen compounds in total, from Thai and Indian mangrove plants. The limonoid WSC-29, belonging to an exclusive class of limonoids in mangrove plants of the genus Xylocarpus, was found to exhibit potent inhibition of tumor growth against the transplanted triple-negative breast cancer cell line MDA-MB-453 in nude mice. Based on the target against triple-negative breast cancers and the utilization of modern analytic techniques, including high performance liquid chromatography, liquid chromatography/mass spectrometry, nuclear magnetic resonance spectroscopy, single-crystal X-ray diffraction, and circular dichroism spectrum, etc., this proposal aims to prospect natural limonoid compounds with novel structures and targeted antitumor activities from Thai and Indian mangrove plants. Afterwards, structure diversity-oriented synthesis and antitumor activity evaluation in vivo and in vitro will be investigated to find new drug candidates against triple-negative breast cancers.