Department of Internal Medicine, Medical Clinic III, Clinic for Hematology, Oncology and Palliative Care, University Medical Center Rostock, Ernst-Heydemann-Strasse 6, 18057, Rostock, Germany.
Institute of Chemistry - Organic Chemistry, University of Rostock, Albert-Einstein-Str. 3 A, 18059, Rostock, Germany.
ChemMedChem. 2022 Jul 19;17(14):e202200162. doi: 10.1002/cmdc.202200162. Epub 2022 May 23.
Spirooxindole-1,3-oxazines are a small and structurally unique class of spirooxindole alkaloids. To date, only four of these compounds have been isolated from natural sources, and their biological properties remained unknown thus far. Dioxyreserpine is a synthetic spirooxindole-1,3-oxazine, that can readily be prepared from the Rauvolfia alkaloid (-)-reserpine by catalytic photooxygenation. While dioxyreserpine itself was now identified as a moderately effective antitumoral agent, structurally modified analogs of it emerged as a new class of highly potent and selective growth inhibitors of various human cancers, including pancreatic cancers. Systematic structural optimization ultimately led to an inhibitor displaying low-micromolar IC -values against six cancer cell lines as well as selective apoptosis induction in vitro.
螺环氧化吲哚-1,3-恶嗪是一类结构较小且独特的螺环氧化吲哚生物碱。迄今为止，这些化合物中只有四种从天然来源中分离出来，其生物特性至今仍不清楚。二氧去甲乌药碱是一种合成的螺环氧化吲哚-1,3-恶嗪，可以通过催化光氧化很容易地从 Rauvolfia 生物碱（-）-去甲乌药碱中制备得到。虽然二氧去甲乌药碱本身被鉴定为一种中等有效的抗肿瘤剂，但它的结构修饰类似物作为一类新的高度有效和选择性的人类癌症（包括胰腺癌）生长抑制剂出现。系统的结构优化最终导致了一种抑制剂，对六种癌细胞系的 IC -值低至微摩尔级，并且在体外选择性诱导细胞凋亡。
