Synthesis, Bacteriostatic and Anticancer Activity of Novel Phenanthridines Structurally Similar to Benzo[c] phenanthridine Alkaloids

0495765 - ÚEB 2019 RIV CH eng J - Journal Article
Lasák, J. - Motyka, K. - Kryštof, Vladimír - Stýskala, J.
Synthesis, Bacteriostatic and Anticancer Activity of Novel Phenanthridines Structurally Similar to Benzo[c] phenanthridine Alkaloids.
Molecules. Roč. 23, č. 9 (2018), č. článku 2155. E-ISSN 1420-3049
R&D Projects: GA MŠMT(CZ) LO1304
Institutional support: RVO:61389030
Keywords : topoisomerase-ii inhibitor * biaryl coupling reaction * biological evaluation * chelerythrine * sanguinarine * nk109 * derivatives * analogs * quaternary * arylation * phenanthridines * benzo[c]phenanthridines * radical cyclization * antiproliferative * antibacterial activity
OECD category: Organic chemistry
Impact factor: 3.060, year: 2018

In this study, we report the synthesis, antibacterial and anticancer evaluation of 38 novel phenanthridines that were designed as analogs of the benzo[c] phenanthridine alkaloids. The prepared phenanthridines differ from the benzo[c] phenanthridines in the absence of a benzene A-ring. All novel compounds were prepared from 6-bromo-2-hydroxy-3-methoxybenzaldehyde in several synthetic steps through reduction of Schiff bases and accomplished by radical cyclization. Twelve derivatives showed high antibacterial activity against Bacillus subtilis, Micrococcus luteus and/or Mycobacterium vaccae at single digit micromolar concentrations. Some compounds also displayed cytotoxicity against the K-562 and MCF-7 cancer cell lines at as low as single digit micromolar concentrations and were more potent than chelerythrine and sanguinarine. The active compounds caused cell-cycle arrest in cancer cells, increased levels of p53 protein and caused apoptosis-specific fragmentation of PARP-1. Biological activity was connected especially with the presence of the N-methyl quaternary nitrogen and 7-benzyloxy substitution (compounds 7i, 7j, 7k, and 7l) of phenanthridine.
Permanent Link: http://hdl.handle.net/11104/0288686