Synthesis and Antitumor Activity of a Series of Novel 1-Oxa-4-Azaspiro[4,5]Deca-6,9-Diene-3,8-Dione Derivatives.

Funding Source

Xavier University of Louisiana, National Institutes of Health

Grant Number

2017 CDLZ-S34, 2G12MD007595


Department of Chemistry

Document Type


Publication Date



A series of novel 1-oxa-4-azaspiro[4.5]deca-6,9-diene-3,8-diones were designed and synthesized by using 4-aminophenol and α-glycolic acid or lactic acid as starting materials in three or four steps. The key step is the metal-catalyzed oxidative cyclization of the amide to 1-oxa-4-azaspiro[4.5]deca-6,9-diene-3,8-diones (10a and 10b), the reaction conditions of which are investigated and optimized. The anticancer activity of 17 1-oxa-4-azaspiro[4.5] deca-6,9-diene-3,8-dione derivatives was evaluated. Preliminary results showed that 15 compounds have moderate to potent activity against human lung cancer A549, human breast cancer MDA-MB-231, and human cervical cancer HeLa cancer cell lines. Among them, compounds 11b and 11h were the most potent against A549 cell line with 0.18 and 0.19 µM of IC50, respectively; compounds 11d, 11h, and 11k showed the most potent cytotoxicity against MDA-MB-231 cell line with 0.08, 0.08, and 0.09 µM of IC50, respectively, while the activities of 11h, 11k, and 12c against HeLa cell line were the most potent with 0.15, 0.14, and 0.14 µM of IC50, respectively. Compound 11h is a promising candidate for further development, which emerged as the most effective compound overall against the three tested cancer cell lines.


DOI: 10.3390/molecules24050936

PubMed ID: 30866506

Funding text

Funding: This work was funded by Sichuan University-Lu Zhou Strategic Cooperation Projects (2017 CDLZ-S34) (L. He) and in part supported by NIH RCMI program at Xavier University of Louisiana through Grant (2G12MD007595) (G. Wang).