Singh Chetan Paul, Sharma Priyanka, Ahmed Manzoor, Kumar Diljeet, Sharma Yogesh Brijwashi, Samanta Jayanta, Ahmed Zabeer, Shukla Sanket Kumar, Hazra Abhijit, Bharitkar Yogesh P
CSIR-Indian Indian Institute of Integrative Medicine, Canal Road, Jammu 180001, India.
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
ACS Omega. 2023 Sep 14;8(38):35283-35294. doi: 10.1021/acsomega.3c05020. eCollection 2023 Sep 26.
Natural products possess unique and broader intricacies in the chemical space and have been essential for drug discovery. The crucial factor for drug discovery success is not the size of the library but rather its structural diversity. Although reports on the number of new structurally diverse natural products (NPs) have declined recently, researchers follow the next logical step: synthesizing natural product hybrids and their analogues using the most potent tool, diversity-oriented synthesis (DOS). Here, we use weed as a source of parthenin for synthesis of novel dispiro-pyrrolizidino/thiopyrrolizidino-oxindolo/indanedione natural product hybrids of parthenin via chemo-, regio-, and stereoselective azomethine ylide cycloaddition. All synthesized compounds were characterized through a detailed analysis of one-dimensional (1D) and two-dimensional (2D) NMR and HRMS data, and the stereochemistries of the compounds were confirmed by X-ray diffraction analysis. All compounds were evaluated for their cytotoxicity against four cell lines (HCT-116, A549, Mia-Paca-2, and MCF-7), and compound inhibited the HCT-116 cells with an IC of 5.0 ± 0.08 μM.
天然产物在化学空间中具有独特且更广泛的复杂性，对药物发现至关重要。药物发现成功的关键因素不是文库的规模，而是其结构多样性。尽管最近关于新的结构多样的天然产物（NPs）数量的报道有所下降，但研究人员采取了下一步合理措施：使用最强大的工具——多样化导向合成（DOS）来合成天然产物杂合体及其类似物。在此，我们以杂草作为蜂斗菜素的来源，通过化学、区域和立体选择性的甲亚胺叶立德环加成反应，合成了新型的双螺环吡咯里西啶/硫代吡咯里西啶 - 氧化吲哚/茚二酮类蜂斗菜素天然产物杂合体。所有合成的化合物都通过对一维（1D）和二维（2D）核磁共振以及高分辨质谱数据的详细分析进行了表征，并且化合物的立体化学结构通过X射线衍射分析得以确认。所有化合物都针对四种细胞系（HCT - 116、A549、Mia - Paca - 2和MCF - 7）进行了细胞毒性评估，化合物对HCT - 116细胞具有抑制作用，其半数抑制浓度（IC）为5.0±0.08μM。
