Efficient one-pot synthesis of anti-HIV and anti-tumour β-carbolines

Kusurkar, Radhika S.; Goswami, Shailesh K.

doi:10.1016/j.tet.2004.04.079

“…CDH of the resulting tetrahydroharmin by 1 d afforded the target alkaloid, with an overall yield of 57 % (see the Supporting Information for details). In comparison with other known methods,25 this concise synthesis of harmine using commercially available materials is high‐yielding and less wasteful under mild reaction conditions.…”

Section: Methodsmentioning

confidence: 95%

Acceptorless Dehydrogenation of Nitrogen Heterocycles with a Versatile Iridium Catalyst

Wu

¹

,

Talwar

²

,

Johnston

³

et al. 2013

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“…However, the efficacy of treatment with apoptotic drugs is limited by their toxicity to normal cells [55]. Because of the neurotoxic and co‐mutagenic properties of norharman [56,57], many studies have been focused on the structure modification of norharman to enhance its antitumour activities and to decrease the acute toxic and neurotoxic effects of the compound documented in recent years [49,50,58]. Structurally, norharman, as the β‐carboline nucleus, can serve as the molecular backbone for the design and synthesis of β‐carboline derivatives.…”

Section: Discussionmentioning

confidence: 99%

Identification of norharman as the cytotoxic compound produced by the sponge (Hymeniacidon perleve)‐associated marine bacterium Pseudoalteromonas piscicida and its apoptotic effect on cancer cells

Zheng

¹

,

Yan

²

,

Han

³

et al. 2006

Biotech and App Biochem

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Marine invertebrates harbour a wealth of micro-organisms in their bodies. Most of these micro-organisms can catabolize antibiotic compounds as chemical-defence compounds. These compounds not only play an important protective role for their producer and for their hosts, but also have high potential in medicinal applications. In order to discover natural anticancer products, 29 marine bacterial strains have been isolated from the sponge Hymeniacidon perleve, samples of which were collected from the intertidal zone during low tide off Nanji island in Eastern China. By means of a cytotoxicity bioassay, one strain, NJ6-3-1, with significant cytotoxic activity, was selected for culture in a 30-litre fermentation tank. The major cytotoxic compound in the metabolites of NJ6-3-1, separated by means of a bioassay-guided fractionation process, has been identified as norharman (a beta-carboline alkaloid) by electron-impact MS and NMR analyses. Norharman showed cytotoxicity towards both the HeLa cervical-cancer cell line and the BGC-823 stomach-cancer cell line, with an IC(50) of 5 microg/ml. Several methods were used to study the mechanism by which norharman is cytotoxic to HeLa cells. By means of an Acridine Orange/ethidium bromide dual-staining assay, condensation of chromatin was observed. A TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) assay showed degradation of DNA. Flow-cytometric analysis indicated that norharman could arrest cells at the G(2)/M phase of the cell cycle. These results demonstrate the cytotoxic mechanism of norharman involves the induction of apoptosis in HeLa cells.

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“…CDH of the resulting tetrahydroharmin by 1 d afforded the target alkaloid, with an overall yield of 57 % (see the Supporting Information for details). In comparison with other known methods, [25] this concise synthesis of harmine using commercially available materials is highyielding and less wasteful under mild reaction conditions. Preliminary mechanistic studies of CDH of 2 a and 4 b shed light on how these CDH reactions may take place (see the Supporting Information for details).…”

Section: Methodsmentioning

confidence: 99%