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

Molecules

Andrea Ghelli Luserna di Ror๠ Giorgia Simonetti¹  Giovanni Martinelli¹  Fabio Mantellini²  Joseph Durante²  Samantha Bruno³  Dario Telese⁴  Gabriele Micheletti⁴  Carla Boga⁴  Paolo Caruana⁴  Natalia Calonghi⁵ 

[1] Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori”—IRST S.r.l., 47014 Meldola (FC), Italy;Department of Biomolecular Sciences, University of Urbino “Carlo Bo”, Via I Maggetti 24, 61029 Urbino (PU), Italy;Department of Experimental, Diagnostic and Specialty Medicine, Institute of Hematology and Medical Oncology “L. and A. Seràgnoli”, University of Bologna, 40138 Bologna, Italy;Department of Industrial Chemistry “Toso Montanari”, Alma Mater Studiorum—Università di Bologna, Viale del Risorgimento 4, 40136 Bologna, Italy;Department of Pharmacy and Biotechnology, University of Bologna, 40121 Bologna, Italy;

关键词: cancer;    tryptamine;    leukemias;    chloral;    pyrimidine;   

DOI  :  10.3390/molecules26030683

来源: DOAJ

【 摘 要 】

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).

【 授权许可】

Unknown