癌症多年來一直位居十大死因之列，其中乳腺癌是女性中最常見的癌症之一，也是女性癌症相關死亡的主要原因之一。乳腺癌可分為四個亞型之一是三陰性乳腺癌(TNBC)，其特點是高死亡率、高復發率、高轉移率和強烈的耐藥性，從而大大降低了治療的有效性。 本報告聚焦於一系列N-(pyrimidin-2-yl)indolin-6-amine衍生物的合成。我們根據化合物結構與生物活性之間的關係設計了所需的吲哚衍生物類似物。通過調整分子結構以增強化合物的生物活性，我們成功地確定並合成了化合物PN009。該化合物被發現對MDA-MB-231具有最強的活性，表明將branched adamantane引入到pyrimidin-6-yl位置有利於抑制癌細胞生長。此外，PN009還顯示可以減少癌細胞遷移並抑制細胞模型中的管狀結構形成。 總之，這種化合物在三陰性乳腺癌細胞(MDA-MB-231)中表現出抗增殖效果，IC50範圍大約在10-20 μM左右，我們對探索其作為新化學實體在藥物開發領域的潛力感到興奮。 ;Cancer has consistently ranked among the top ten leading causes of death for many years, with breast cancer being one of the most prevalent cancers in women and a major contributor to female cancer-related fatalities. Breast cancer is divided into four subtypes, one of which is triple-negative breast cancer (TNBC), which is characterized by high mortality, high recurrence rate, high metastasis rate, and strong drug resistance, thus greatly reducing the effectiveness of treatment. This report focuses on the synthesis of a series of N-(pyrimidin-2-yl)indolin-6-amine derivatives. The desired analogues of indoline derivatives are designed based on their relationship between compound structures and their biological activities. By adjusting molecular structures to enhance compound bioactivity, we successfully identified and prepared the compound PN009. It was found to be the most active compound against MDA-MB-231, suggesting that the introduction of branched adamantane substituent into position pyrimidin-6-yl would favor cancer cell growth inhibition. Alternatively, PN009 was shown to reduce cancer cell migration and inhibit tube formation in cell models. In summary, this compound demonstrated anti-proliferative effects in triple-negative breast cancer cells (MDA-MB-231), the IC50 range is around 10-20 μM, and we are excited to explore its potential in the field of drug development as a new chemical entity.
