2. Academic Validation
  3. Synthesis and preliminary evaluation of 3-thiocyanato-1H-indoles as potential anticancer agents

Synthesis and preliminary evaluation of 3-thiocyanato-1H-indoles as potential anticancer agents

  • Eur J Med Chem. 2016 Aug 8:118:21-6. doi: 10.1016/j.ejmech.2016.04.039.
Margiani P Fortes 1,  Paulo B N da Silva 2,  Teresinha G da Silva 3,  Teodoro S Kaufman 4,  Gardenia C G Militão 2,  Claudio C Silveira 5
Affiliations

Affiliations

  • 1 Departamento de Química, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.
  • 2 Universidade Federal de Pernambuco, Departamento de Fisiologia e Farmacologia, CCB R. Prof. Moraes Rego, Cidade Universitária, 50670-901 Recife, PE, Brazil.
  • 3 Universidade Federal de Pernambuco, Departamento de Antibióticos, CCB R. Prof. Moraes Rego, Cidade Universitária, 50670-901 Recife, PE, Brazil.
  • 4 Instituto de Química Rosario (IQUIR, CONICET-UNR), Suipacha 531, 2000 Rosario, Argentina. Electronic address: kaufman@iquir-conicet.gov.ar.
  • 5 Departamento de Química, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil. Electronic address: silveira@quimica.ufsm.br.
PMID: 27116711 DOI: 10.1016/j.ejmech.2016.04.039
Abstract

A novel series of twenty 3-thiocyanato-1H-indoles, carrying diversification at positions N-1, C-2 and C-5 of the heterocyclic core, were synthesized; their antiproliferative activity against four human Cancer cell lines (HL60, HEP-2, NCI-H292 and MCF-7) was evaluated, employing doxorubicin as positive control. Indole, N-methylindole and 2-(4-chlorophenyl)-N-methylindole demonstrated to be essentially inactive, whereas several of their congener 3-thiocyanato-1H-indoles displayed good to excellent levels of potency (IC50 ≤ 6 μM), while being non-hemolytic. N-Phenyl-3-thiocyanato-1H-indole and 1-methyl-2-(4-chlorophenyl)-3-thiocyanato-1H-indole showed good to high potency against all the cell lines. On the Other side, the N-(4-chlorophenyl)-, 2-(4-chlorophenyl)- and 2-phenyl- 3-thiocyanato-1H-indole derivatives were slightly less active against the test cell lines. Overall, these results suggest that the indole-3-thiocyanate motif can be suitably decorated to afford highly cytotoxic compounds and that the substituted indole can be employed as a useful scaffold toward more potent compounds.

Keywords

3-Thiocyanato-1H-indoles; Bioactive heterocycles; Cytotoxic compounds; HL60 and HEP-2; NCI-H292 and MCF-7 cells.

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