Semisynthesis of Novel Dispiro-pyrrolizidino/thiopyrrolizidino-oxindolo/indanedione Natural Product Hybrids of Parthenin Followed by Their Cytotoxicity Evaluation

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 Parthenium hysterophorus 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 6 inhibited the HCT-116 cells
with an IC50 of 5.0 ± 0.08 μM.