The synthesis and in vitro anticancer activity of novel β-carbolines is reported. New tryptamines have been prepared via hetero-Diels-Alder reaction of nitrosoalkenes with indoles and used to prepare functionalized β-carbolines by the Pictet-Spengler approach. These included 6-substituted-β-carboline-3-carboxylates and 3-(1H-tetrazol-5-yl)-β-carbolines, whose synthesis is reported for the first time. Carboline-3-carboxylates derived from l-tryptophan methyl ester were also prepared. The structural diversity that was achieved allowed the discovery of impressive activities against a range cancer cell lines with the selectivity depending on the type of substitution pattern of the β-carboline core. We have identified at least one β-carboline derivative with GI50 ≤ 1 μM for each of the following human tumor cell lines: glioblastoma (U251), melanona (UACC-61), breast (MCF-7), ovarian expressing multiple-drug-resistance phenotype 4 (NCI-ADR/RES), renal (786-0), lung (NCI-H460), ovarian cancer (OVCAR-3), leukemia (K-562) and colon (HT29). These results demonstrated that the new β-carboline derivatives are very promising anticancer agents.
Keywords: Anti-cancer agents; Cycloaddition; Nitrosoalkenes; Tetrazoles; β-Carbolines.
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