Straightforward synthesis, characterization, and cytotoxicity evaluation of hybrids of natural alkaloid evodiamine/rutaecarpine and thieno[2,3-d]pyrimidinones

Abstract

Dozens of hybrids of natural alkaloid evodiamine/rutaecarpine and thieno[2,3-d]pyrimidinones were synthesized in a straightforward method by condensation of substituted 2H-thieno[2,3-d][1, 3]oxazine-2,4(1H)-diones or N-methyl-2H-thieno[2,3-d][1, 3]oxazine-2,4(1H)-dione with 3,4-dihydro-β-carbolines. In vitro cytotoxic assay discovered that compounds 9a, 10e, 11a, 11d, 11f, and 12a could induce antiproliferation against four different types of human cancer cells while compounds 10f and 12e were inactive. Notably, compound 11a displayed potent cell cytotoxicity for human non-small cell lung cancer cells A549, PC-9, human prostate cancer cells PC-3, and human breast cancer cell line MCF-7. Furthermore, compound 11a exhibited strong colony formation inhibition to A549 cells. These results unfold potential anticancer therapeutic applications of hybrids of thieno[2,3-d]pyrimidinones and quinazolinones.

Graphical Abstract

Keywords:

• Thieno[2,3-d]pyrimidinone
• evodiamine
• rutaecarpine
• hybrid
• cytotoxicity

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by 12th Chinese Recruitment Program of Global Experts (Thousand Talents Program) and Research Program of Shanghai Normal Univeristy (DYL201702).