Search Results (3)

The tumor suppressor p53 is inactivated by mutation in approximately 50% of human cancers. Small molecules that bind and stabilize those mutants may represent effective anticancer drugs. Herein, we report the tumor cell growth inhibitory activity of carbazole alkaloids and amino derivatives, as well as their potential activation of p53. Twelve aminocarbazole alkaloids were semi-synthesized from heptaphylline (1), 7-methoxy heptaphylline (2), and 7-methoxymukonal (3), isolated from Clausena harmandiana, using a reductive amination protocol. Naturally-occurring carbazoles 1–3 and their amino derivatives were evaluated for their potential effect on wild-type and mutant p53 activity using a yeast screening assay and on human tumor cell lines. Naturally-occurring carbazoles 1–3 showed the most potent growth inhibitory effects on wild-type p53-expressing cells, being heptaphylline (1) the most promising in all the investigated cell lines. However, compound 1 also showed growth inhibition against non-tumor cells. Conversely, semi-synthetic aminocarbazole 1d showed an interesting growth inhibitory activity in tumor cells expressing both wild-type and mutant p53, exhibiting low growth inhibition on non-tumor cells. The yeast assay showed a potential reactivation of mutant p53 by heptaphylline derivatives, including compound 1d. The results obtained indicate that carbazole alkaloids may represent a promising starting point to search for new mutp53-reactivating agents with promising applications in cancer therapy. Full article

The title compound (2) was prepared in high yield by catalytic transfer hydrogenation of the 6-nitro precursor (1), using hydrazine hydrate as the hydrogen source. Under the conditions employed, the ester groups remain unaffected. The new compound was fully characterised by elemental analysis, ¹H-NMR, ¹³C-NMR, MS and HRMS data. Full article

The reactions in benzene of 9-alkyl-3-aminocarbazoles with ethyl-3-oxobutanoateyielded ethyl-3-[(9-alkyl-9H-carbazol-3-yl)amino]but-2-enoate condensation products or N-(9-ethyl-9H-carbazol-3-yl)-3-oxobutanamide acylation products. The condensation productswere cyclized to the corresponding 4,7-dihydro-pyrido[2,3-c]-carbazol-1-ones upon heatingin mineral oil at 240-250 °C. The structures of the synthesized compounds were investigatedby IR, mass spectrometry, ¹H- and ¹³C-NMR spectroscopy and MM2 molecular mechanicsand AM1 semi-empirical quantum mechanical methods. Full article