Synthesis and Cytoxicity of Sempervirine and Analogues

Abstract

Sempervirine and analogues were synthesized using a route featuring Sonogashira and Larock Pd-catalyzed reactions. Structure–activity relationships were investigated using three human cancer cell lines. 10-Fluorosempervirine is the most potently cytotoxic member of the family yet described.

Aza-Annulation of 1,2,3,4-Tetrahydro-β-carboline Derived Enaminones and Nitroenamines: Synthesis of Functionalized Indolizino[8,7-b]indoles, Pyrido[1,2-a:3,4-b′]diindoles, Indolo[2,3-a]quinolizidine-4-ones and Other Tetrahydro-β-carboline Fused Heterocycles

“…6a Du and co-workers have recently reported a novel synthetic approach to functionalized indolo[2,3- a ]quinolizidones via N-heterocyclic carbene-catalyzed annulations of β-carboline-derived enamino ester with enals. 6b,24…”

Ru(II) coordination compounds of N N bidentate chelators with 1,2,3 triazole and isoquinoline subunits: Synthesis, spectroscopy and antimicrobial properties

“…Trimethylsilylacetylene (GFS Chemicals), benzyl bromide and isoquinoline reactants (Oakwood Chemical), Ru and Pd compounds (Oakwood), all other reactants (Aldrich), reaction solvents (Fisher Scientific), and NMR solvents (Cambridge Isotopes) were used as purchased. 1-and 3-isoquinolinyl triflates [27,28] and 1-and 3trimethylsilylethynylisoquinolines [29,30] were prepared as previously described. Microorganisms were prepared from freeze-dried samples purchased from ATCC (Bacillus subtilus (ATCC 6051), Staphylococcus epidermidis (ATCC 14990), Escherichia coli (ATCC 25922), Enterobacter aerogenes (ATCC 13048), Candida albicans (ATCC 90028).…”

“…N1-benzyl-and phenylbenzyl-substituted analogs of chelators 1-iqtz and 3-iqtz were each prepared using a three step synthetic sequence (Scheme 1). Following triflation of commercially-available 1-hydroxyisoquinoline and isoquinolin-3(2H)-one precursors, [27,28] Sonogashira coupling was used to prepare 1-and 3trimethylsilylethynylisoquinolines. [27][28][29][30] An efficient three-step one-pot transformation involving K 2 CO 3 promoted TMS deprotection, benzylic azide substitution and CuAAC was used to prepare the desired chelators in 71-88% isolated yields.…”

“…Following triflation of commercially-available 1-hydroxyisoquinoline and isoquinolin-3(2H)-one precursors, [27,28] Sonogashira coupling was used to prepare 1-and 3trimethylsilylethynylisoquinolines. [27][28][29][30] An efficient three-step one-pot transformation involving K 2 CO 3 promoted TMS deprotection, benzylic azide substitution and CuAAC was used to prepare the desired chelators in 71-88% isolated yields. [39][40][41][42] In order to directly compare the influence of the isoquinoline subunits relative to the pyridine subunit on coordination, spectroscopic and antimicrobial properties, pytz chelators with identical N1substituents were also similarly prepared (Scheme S1).…”

Sempervirine Mediates Autophagy and Apoptosis via the Akt/mTOR Signaling Pathways in Glioma Cells

“…in 1949; its structure and chemical properties have been reported by Nature and J AM CHEM SOC ( Goutarel et al, 1948 ; Bentley and Stevens, 1949 ; Woodward and Witkop, 1949 ; Ska, 2006 ). Since 2016, J AM CHEM SOC and other journals reported its synthesis and chemical structure modification ( Pan et al, 2016 ; Sucunza et al, 2016 ; Kerkovius and Kerr, 2018 ). Previous research showed that sempervirine can distinguish between cancer and normal DNAs, and it can inhibit YC8 lymphoma cells and Ehrlich ascites carcinoma cells in vitro ( Beljanski and Beljanski, 1986 ).…”