Department of Pharmaceutical Engineering and Technology, Indian Institute of Technology (Banaras Hindu University), Varanasi 221005, Uttar Pradesh, India.
Department of Biological Sciences, National Institute of Pharmaceutical Education and Research, Hyderabad 500 037, Telangana, India.
Steroids. 2023 Dec;200:109315. doi: 10.1016/j.steroids.2023.109315. Epub 2023 Sep 29.
The cytotoxic dichloromethane-methanol bark extract of Dysoxylum malabaricum was subjected to bioassay-guided fractionation, followed by systematic dereplication to focus on the identification of new compounds. From the bark of Dysoxylum malabaricum, two new cycloartane-type triterpenoids were isolated in addition to two previously known triterpenoids. The structures and absolute configurations of the isolated compounds were elucidated unambiguously via NMR, HRESIMS data, and electronic circular dichroism calculations. The isolated compounds were tested for their cytotoxic potential against the panel of breast, lung, and hypopharynx cancer cell lines and displayed notable cytotoxicity against breast cancer cell lines. Compound 3 exhibited the most potent cytotoxic effect with an IC 14 µM against MCF-7 cell lines and induced cell cycle arrest. Through western blot and cell cycle analysis, it was revealed that compound 3 halts the G0/G1 phase of the cell cycle by inhibiting CDC20 and CDC25 enzymes.
麻疯树的细胞毒性二氯甲烷-甲醇树皮提取物经过生物活性导向分离，然后进行系统去重复化处理，重点是鉴定新化合物。从麻疯树的树皮中分离出两种新的环阿尔廷型三萜，此外还有两种先前已知的三萜。通过 NMR、HRESIMS 数据和电子圆二色性计算，明确阐明了分离化合物的结构和绝对构型。对分离得到的化合物进行了针对乳腺癌、肺癌和下咽癌细胞系的细胞毒性测试，显示出对乳腺癌细胞系的显著细胞毒性。化合物 3 表现出最强的细胞毒性，对 MCF-7 细胞系的 IC 50 为 14 μM，并诱导细胞周期停滞。通过 Western blot 和细胞周期分析，发现化合物 3 通过抑制 CDC20 和 CDC25 酶来阻止细胞周期的 G0/G1 期。
