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

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Pavel LasákJakub Stýskala

Abstract

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 Bacillussubtilis, Micrococcusluteus and/or Mycobacteriumvaccae 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.

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Citations

Apr 16, 2020·Organic & Biomolecular Chemistry·Benyao FangJunbiao Chang
Nov 17, 2019·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Josef Jampilek
Sep 17, 2020·Chemistry, an Asian Journal·Savita B NagodeNamrata Rastogi
Jul 22, 2021·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·José Tiago M CorreiaMárcio W Paixão

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Methods Mentioned

BETA
column chromatography
NMR
flow cytometry

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