In this study, we report the synthesis, antibacterial and anticancer evaluation of 38 novel phenanthridines that were designed as analogs of the benzo[]phenanthridine alkaloids. The prepared phenanthridines differ from the benzo[]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 , and/or 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 -methyl quaternary nitrogen and 7-benzyloxy substitution (compounds , , , and ) of phenanthridine.
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| http://dx.doi.org/10.3390/molecules23092155 | DOI Listing |
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Article Synopsis
- - N-methyl-d-aspartate receptors (NMDARs) are key players in excitatory neurotransmission in the central nervous system and are linked to several neurological disorders, making them a target for potential therapies.
- - The study investigates the effects of chelerythrine (CHE), an alkaloid with various biological activities, on NMDAR function, revealing that CHE suppresses NMDA-induced currents in neurons and facilitates desensitization of GluN2B NMDARs.
- - The inhibitory action of CHE on GluN2B NMDARs is independent of protein kinase C activity and is influenced by pH, with specific interactions identified at the receptor's M3 α-helical
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