- New 6- and 7-heterocyclyl-1H-indole derivatives as potent tubulin assembly and cancer cell growth inhibitors
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We designed new 3-arylthio- and 3-aroyl-1H-indole derivatives 3–22 bearing a heterocyclic ring at position 5, 6 or 7 of the indole nucleus. The 6- and 7-heterocyclyl-1H-indoles showed potent inhibition of tubulin polymerization, binding of colchicine to tubulin and growth of MCF-7 cancer cells. Compounds 13 and 19 inhibited a panel of cancer cells and the NCI/ADR-RES multidrug resistant cell line at low nanomolar concentrations. Compound 13 at 50 nM induced 77% G2/M in HeLa cells, and at 20 nM caused 50% stable arrest of mitosis. As an inhibitor of HepG2 cells (IC50 = 20 nM), 13 was 4-fold superior to 19. Compound 13 was a potent inhibitor of the human U87MG glioblastoma cells at nanomolar concentrations, being nearly one order of magnitude superior to previously reported arylthioindoles. The present results highlight 13 as a robust scaffold for the design of new anticancer agents.
- La Regina, Giuseppe,Bai, Ruoli,Coluccia, Antonio,Naccarato, Valentina,Famiglini, Valeria,Nalli, Marianna,Masci, Domiziana,Verrico, Annalisa,Rovella, Paola,Mazzoccoli, Carmela,Da Pozzo, Eleonora,Cavallini, Chiara,Martini, Claudia,Vultaggio, Stefania,Dondio, Giulio,Varasi, Mario,Mercurio, Ciro,Hamel, Ernest,Lavia, Patrizia,Silvestri, Romano
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- Rapid Syntheses of Heteroaryl-Substituted Imidazo[1,5-a]indole and Pyrrolo[1,2-c]imidazole via Aerobic C2-H Functionalizations
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Here we report an aerobic Pd(0) catalyzed C2-H functionalization of indoles and pyrroles with tethered N-methoxylamide as the directing group. A Pd(0)-initiated mechanism overcomes the directing or poisoning effect from a wide range of heterocycles including pyridine, pyrimidine, and thiazole. The imidazo[1,5-a]indole products are transformed to bioactive analogs after one-step manipulations, demonstrating the potential utility of this reaction in drug discovery.
- Kong, Wei-Jun,Chen, Xingrong,Wang, Mingming,Dai, Hui-Xiong,Yu, Jin-Quan
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supporting information
p. 284 - 287
(2018/01/17)
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- A general method for Suzuki-Miyaura coupling reactions using lithium triisopropyl borates
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Conditions for the Suzuki-Miyaura coupling of lithium triisopropyl borates are reported, as well as a procedure for a one-pot lithiation, borylation, and subsequent Suzuki-Miyaura coupling of various heterocycles with aryl halides. These borate species are much more stable toward protodeboronation than the corresponding boronic acids and can conveniently be stored on benchtop at room temperature.
- Oberli, Matthias A.,Buchwald, Stephen L.
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supporting information
p. 4606 - 4609
(2012/10/30)
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- SYNTHESIS OF 5-ARYLATED INDOLES VIA PALLADIUM-CATALYZED CROSS-COUPLING REACTION OF 5-INDOLYLBORONIC ACID WITH ARYL AND HETEROARYL HALIDES
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Palladium(0)-catalyzed cross-coupling reaction of 5-indolylboronic acid with various aryl and heteroaryl halides results in regioselective formation of 5-arylated indoles in good yields.
- Yang, Youhua,Martin, Arnold R.
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p. 1395 - 1398
(2007/10/02)
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