- Design, synthesis and biological evaluation of a novel library of antimitotic C2-aroyl/arylimino tryptamine derivatives that are also potent inhibitors of indoleamine-2, 3-dioxygenase (IDO)
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A novel library of C2-substituted tryptamines (based on diverse C2-aroyl/arylimino indoles and indole-diketopiperazine hybrids) possessing antimitotic properties were designed, synthesized and screened for their inhibitory activity against tubulin polymerization, and against proliferation of A549 lung cancer, HeLa cervical cancer, MCF7 breast cancer and HePG2 liver cancer cell lines. The design of molecules were inspired from known antimitotic compounds and natural products. The molecular docking of the designed compounds indicated that they bind to the colchicin binding site of tubulin. They were synthesized by a unique iodine catalysed oxidative ring opening reaction of 1-aryltetrahydro-β-carbolines. Among the compounds synthesized quite a few compounds induced cytotoxicity on the cancer cells by disrupting the tubulin polymerization. They were found to be non-toxic for healthy cells. Immuno Fluorescence study for the most active molecules (between ~6 μM concentration) against A549 and HeLa cells demonstrated complete disruption and shrinkage of the microtubule structures. These compounds also inhibited indoleamine-2, 3-dioxygenase with low micromolar IC50.
- Chauhan, Jyoti,Dasgupta, Moumita,Luthra, Tania,Awasthi, Akanksha,Tripathy, Sayantan,Banerjee, Anindyajit,Paul, Santanu,Nag, Debasish,Chakrabarti, Saikat,Chakrabarti, Gopal,Sen, Subhabrata
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p. 249 - 265
(2018/09/12)
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- Iodine-Catalyzed Metal-Free Oxidative Ring Opening of 1-Aryltetrahydro-β-carbolines: Facile Synthesis of C-2 Aroyl and Aryl Methanimino Indole Derivatives
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Indole derivatives bearing C-2 substituents have garnered a lot of attention due to their diverse biological activities. Various methods forthe synthesis of these compounds have been reported. Inspired by the hydrolysis of imines, an oxidative ring-opening reaction of 1-aryltetrahydro-β-carbolines with catalytic iodine in aqueous hydrogen peroxide, and also in the presence of appropriate amines, is described for the generation of 2-aroyl and arylmethanimine indole derivatives. The reaction proceeds under mild reaction conditions with ethanol as the solvent or under solvent-free conditions, respectively. This metal-free strategy facilitates the formation of the desired substituted C-2 indoles in moderate to excellent yields. The utility of this reaction is demonstrated by a facile multigram-scale synthesis of Luzindole, a selective melatonin receptor antagonist and an investigational drug against depression and disruption of the circadian rhythm.
- Chauhan, Jyoti,Luthra, Tania,Sen, Subhabrata
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p. 4776 - 4786
(2018/09/06)
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- Development of the Pictet-Spengler reaction catalyzed by AuCl 3/AgOTf
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Mild and efficient AuCl3/AgOTf-catalyzed Pictet-Spengler reactions were developed to afford in good yields a variety of tetrahydroisoquinoline and tetrahydro-β-carboline ring systems, which constitute important motifs in biologically active nat
- Youn, So Won
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p. 2521 - 2523
(2007/10/03)
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- Synthesis of 2-acyltetrahydro-β-carbolines by an intramolecular α- amidoalkylation reaction
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2-Acyltetrahydro-β-carbolines 7 have been obtained by cyclization of adducts 5 from imines 3 of tryptamine 1 and aldehydes 2 with acyl chlorides 4 as a result of an intramolecular α-amidoalkylation reaction in the presence of bases as N,N-dimethylaniline or Et3N.
- Venkov, Atanas P.,Boyadjieva, Atanaska K.
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p. 487 - 494
(2007/10/03)
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