Straightforward synthesis, characterization, and cytotoxicity evaluation of hybrids of natural alkaloid evodiamine/rutaecarpine and thieno[2,3-<i>d</i>]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 M. Asif, Int. J. Med. Chem. 2014, 395637 (2014).[PubMed] , [Google Scholar], 3 I. Khan, A. Ibrar, N. Abbas, and A. Saeed, Eur. J. Med. Chem.76, 193 (2014).[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]]oxazine-2,4(1H)-diones or N-methyl-2H-thieno[2,3-d][1 M. Asif, Int. J. Med. Chem. 2014, 395637 (2014).[PubMed] , [Google Scholar], 3 I. Khan, A. Ibrar, N. Abbas, and A. Saeed, Eur. J. Med. Chem.76, 193 (2014).[Crossref], [PubMed], [Web of Science ®] , [Google Scholar]]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.