Synthesis of Novel Tryptamine Derivatives and Their Biological Activity as Antitumor Agents

Abstract

We synthesized five novel tryptamine derivatives characterized by the presence of an azelayl chain or of a 1,1,1-trichloroethyl group, in turn connected to another heterocyclic scaffold. The combination of tryptamin-, 1,1,1-trichloroethyl- and 2-aminopyrimidinyl- moieties produced compound 9 identified as the most active compound in hematological cancer cell lines (IC50 = 0.57–65.32 μM). Moreover, keeping constant the presence of the tryptaminic scaffold and binding it to the azelayl moiety, the compounds maintain biological activity. Compound 13 is still active against hematological cancer cell lines and shows a selective effect only on HT29 cells (IC50 = 0.006 µM) among solid tumor models. Compound 14 loses activity on all leukemic lines, while showing a high level of toxicity on all solid tumor lines tested (IC50 0.0015–0.469 µM).

CDC20 in and out of mitosis: a prognostic factor and therapeutic target in hematological malignancies

“…This evidence and the current knowledge provided the rationale for the development of other specific inhibitors. We have synthesized and tested novel tryptamine derivatives bearing aminopyrimidyl- or imidazolyl- moieties, which are also present in Apcin [ 158 ]. In particular, compound 9, characterized by 2-aminopyrimidyl- and trichloroethyl- moieties, similarly to those in Apcin, showed a preferential efficacy in hematology compared with solid tumor models, and significantly reduced the growth of AML and ALL cells.…”

Targeting Proliferation Signals and the Cell Cycle Machinery in Acute Leukemias: Novel Molecules on the Horizon

“…With the aim of targeting the mitotic checkpoint, we have designed a series of tryptamine derivatives [ 127 ]. Compound 9 , which is characterized by 2-aminopyrimidyl- and trichloroethyl- moieties, similarly to those found in Apcin [ 128 ], a small molecule that blocks the interaction between the anaphase-promoting complex/cyclosome (APC/C) and CDC20 [ 53 ], showed a selective activity against acute leukemia models over solid tumors.…”

Transcriptome-based stemness indices analysis reveals platinum-based chemo-theraputic response indicators in advanced-stage serous ovarian cancer

“…Results of this study revealed that BUB1 and CDC20 had significantly higher expression levels in platinum-sensitive samples than that of platinum-resistant in both two GEO datasets. Accumulating evidence indicates that there is a strong link between abnormal upregulation of CDC20 and various types of tumors [41][42][43]. CDC20 knockdown was shown to sensitize cancer cells to chemotherapy and radiation therapy [44,45].…”