12 junio 2017

Synthesis and Cytotoxicity of a Novel Series of Saframycin-Ecteinascidin Analogs containing Tetrahydro-β-Carboline Moieties.

Eur J Med Chem. 2017 Jul 28.

Resultado de imagen de ecteinascidinLu X, Pan X, Yang Y, Ji M, Chen X, Xiao Z, Liu Z.

State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100050, PR China.

Abstract :

A novel bistetrahydrocarboline heptacyclic skeleton and its twenty derivatives were prepared from l-tryptophan through a 15-step stereospecific route.

The cytotoxicities of these compounds were tested against six human cancer cell lines including HCT-116, HepG2, BGC-823, MCF-7, A2780, and HT-29. Most of the derivatives with amide side chain exhibited the IC50 values at the level of 10-7 M, and a preliminary structure-activity relationship (SAR) was discussed.

Both compound 30 with 2-pyridine amide side chain and compound 14 with phthalamide side chain showed the most potent and broad cytotoxicity towards all six cell lines with the IC50 values at the level of 10-8 M. Molecular docking of compound 30 indicated it bound to minor groove of DNA duplex.

Copyright © 2017 Elsevier Masson SAS