The synthesis and in vitro anticancer activity of novel beta-carbolines is reported. New tryptamines have been prepared via hetero-Diels-Alder reaction of nitrosoalkenes with indoles and used to prepare functionalized beta-carbolines by the Pictet-Spengler approach. These included 6-substituted-beta-carboline-3-carboxylates and 3-(1H-tetrazol-5-yl)-beta-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 beta-carboline core. We have identified at least one beta-carboline derivative with GI(50) < 1 mu M 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 3-carboline derivatives are very promising anticancer agents. (C) 2019 Elsevier Masson SAS. All rights reserved.