Synthesis and preliminary evaluation of 3-thiocyanato-1H-indoles as potential anticancer agents.
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.
Departamento de Química, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil.
Margiani P
MP
Fortes
Universidade Federal de Pernambuco, Departamento de Fisiologia e Farmacologia, CCB R. Prof. Moraes Rego, Cidade Universitária, 50670-901 Recife, PE, Brazil.
Paulo B N
PB
da Silva
Universidade Federal de Pernambuco, Departamento de Antibióticos, CCB R. Prof. Moraes Rego, Cidade Universitária, 50670-901 Recife, PE, Brazil.
Teresinha G
TG
da Silva
Instituto de Química Rosario (IQUIR, CONICET-UNR), Suipacha 531, 2000 Rosario, Argentina. Electronic address: kaufman@iquir-conicet.gov.ar.
Teodoro S
TS
Kaufman
Universidade Federal de Pernambuco, Departamento de Fisiologia e Farmacologia, CCB R. Prof. Moraes Rego, Cidade Universitária, 50670-901 Recife, PE, Brazil.
Gardenia C G
GC
Militão
Departamento de Química, Universidade Federal de Santa Maria, 97105-900 Santa Maria, RS, Brazil. Electronic address: silveira@quimica.ufsm.br.
Claudio C
CC
Silveira
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D004354:Drug Screening Assays, Antitumor; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity
D000970:Antineoplastic Agents; D007211:Indoles
3-Thiocyanato-1H-indoles; Bioactive heterocycles; Cytotoxic compounds; HL60 and HEP-2; NCI-H292 and MCF-7 cells