2. Academic Validation
  3. New 3-tetrazolyl-β-carbolines and β-carboline-3-carboxylates with anti-cancer activity

New 3-tetrazolyl-β-carbolines and β-carboline-3-carboxylates with anti-cancer activity

  • Eur J Med Chem. 2019 Oct 1:179:123-132. doi: 10.1016/j.ejmech.2019.05.085.
Manuela Ribeiro Panice 1,  Susana M M Lopes 2,  Mariana Cecchetto Figueiredo 3,  Ana Lucia T Goes Ruiz 3,  Mary Ann Foglio 3,  Anelise S Nazari Formagio 4,  Maria Helena Sarragiotto 4,  Teresa M V D Pinho E Melo 5
Affiliations

Affiliations

  • 1 Departamento de Química, Universidade Estadual de Maringá, 87020-900, Maringá, PR, Brazil; CQC and Department of Chemistry, University of Coimbra, 3004-535, Coimbra, Portugal.
  • 2 CQC and Department of Chemistry, University of Coimbra, 3004-535, Coimbra, Portugal.
  • 3 Centro Pluridisciplinar de Pesquisas Químicas, Biológicas e Agrícolas (CPQBA), Universidade Estadual de Campinas, 13083-970, Campinas, SP, Brazil.
  • 4 Departamento de Química, Universidade Estadual de Maringá, 87020-900, Maringá, PR, Brazil.
  • 5 CQC and Department of Chemistry, University of Coimbra, 3004-535, Coimbra, Portugal. Electronic address: tmelo@ci.uc.pt.
PMID: 31247374 DOI: 10.1016/j.ejmech.2019.05.085
Abstract

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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