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Total synthesis and antiproliferative activity screening of (±)-aplicyanins A, B and E and related analogs

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The first total synthesis of the indole alkaloids ()-aplicyanins A, B and E, plus seventeen analogs, all in racemic form is reported. Modifications to the parent compound included changing the number of bromine substituents on the indole, the groups on the indole nitrogen (H, Me or OMe), and/or the oxidation level of the heterocyclic core tetrahydropyrimidine. Each compound was screened against three human tumor cell lines, and fourteen of the newly synthesized compounds showed considerable cytotoxicity. The assay results were used to establish structure-activity relationships. These results suggest that the acetyl group moiety on the imine nitrogen, and the bromine at position 5 of the indole, are both critical to activity.

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SÍSA, Miroslav, PLA QUERAL, Daniel, ALTUNA, Marta, FRANCESCH, Andrés, CUEVAS, Carmen, ALBERICIO PALOMERA, Fernando, ÁLVAREZ DOMINGO, Mercedes. Total synthesis and antiproliferative activity screening of (±)-aplicyanins A, B and E and related analogs. _Journal of Medicinal Chemistry_. 2009. Vol. 52, núm. 20, pàgs. 6217-6223. [consulta: 24 de gener de 2026]. ISSN: 0022-2623. [Disponible a: https://hdl.handle.net/2445/56023]

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