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11a-N-tosyl-5-carbapterocarpans: Synthesis, antineoplastic evaluation and in silico prediction of ADMETox properties.
Mendes, Joseane A; Salustiano, Eduardo J; Pires, Carulini de S; Oliveira, Thaís; Barcellos, Julio C F; Cifuentes, Jhonny M C; Costa, Paulo R R; Rennó, Magdalena N; Buarque, Camilla D.
Affiliation
  • Mendes JA; Departamento de Química, Pontifícia Universidade Católica do Rio de Janeiro, Rua Marquês de São Vicente, 225, Gávea, Rio de Janeiro, RJ 22435-900, Brazil.
  • Salustiano EJ; Laboratório de Imunologia Tumoral, Instituto de Bioquímica Médica Leopoldo de Meis, Centro de Ciências da Saúde, Bloco H sala 003, Universidade Federal do Rio de Janeiro, RJ 21941-590, Brazil; Laboratório de Glicobiologia, Instituto de Biofísica Carlos Chagas Filho, Centro de Ciências da Saúde, Bloc
  • Pires CS; Laboratório de Modelagem Molecular e Pesquisa em Ciências Farmacêuticas, Núcleo em Ecologia e Desenvolvimento Sócio-Ambiental de Macaé, Universidade Federal do Rio de Janeiro Campus Macaé Professor Aloísio Teixeira, Macaé, RJ 27965-045, Brazil.
  • Oliveira T; Laboratório de Bioquímica e Biologia Molecular do Câncer, Instituto de Bioquímica Médica Leopoldo de Meis, Centro de Ciências da Saúde, Bloco C sala E1-022, Universidade Federal do Rio de Janeiro, RJ 21941-590, Brazil.
  • Barcellos JCF; Laboratório de Química Bioorgânica, Instituto de Pesquisas de Produtos Naturais, Centro de Ciências da Saúde, Bloco H, Universidade Federal do Rio de Janeiro, RJ 21941-590, Brazil.
  • Cifuentes JMC; Departamento de Química, Pontifícia Universidade Católica do Rio de Janeiro, Rua Marquês de São Vicente, 225, Gávea, Rio de Janeiro, RJ 22435-900, Brazil.
  • Costa PRR; Laboratório de Química Bioorgânica, Instituto de Pesquisas de Produtos Naturais, Centro de Ciências da Saúde, Bloco H, Universidade Federal do Rio de Janeiro, RJ 21941-590, Brazil.
  • Rennó MN; Laboratório de Modelagem Molecular e Pesquisa em Ciências Farmacêuticas, Núcleo em Ecologia e Desenvolvimento Sócio-Ambiental de Macaé, Universidade Federal do Rio de Janeiro Campus Macaé Professor Aloísio Teixeira, Macaé, RJ 27965-045, Brazil. Electronic address: mnrenno@macae.ufrj.br.
  • Buarque CD; Departamento de Química, Pontifícia Universidade Católica do Rio de Janeiro, Rua Marquês de São Vicente, 225, Gávea, Rio de Janeiro, RJ 22435-900, Brazil. Electronic address: camilla-buarque@puc-rio.br.
Bioorg Chem ; 80: 585-590, 2018 10.
Article in En | MEDLINE | ID: mdl-30036814
11a-N-tosyl-5-carbapterocarpans (5a-c and 6a-c), 9-N-tosyl-4,4a,9,9a-tetrahydro-3H-carbazole (7), 11a-N-tosyl-5-carbapterocarpen (8) analogues of LQB-223 (4a), were synthesized through palladium catalyzed azaarylation of substituted dihydronaphtalenes (14a-c) and cyclohexadiene (15), respectively, with N-tosyl-o-iodoaniline (11). In order to understand the role of the N-tosyl moiety for the pharmacological activity, the azacarbapterocarpen (9) was also synthesized by Fischer indol reaction. The structural requirements at the A and D-rings for the antineoplastic activity toward human leukemias and breast cancer cells were evaluated as well. Substitutions on the A-ring of 4a and analogues alter the effect on different breast cancer subtypes. On the other hand, A-ring is not essential for antileukemic activity since compound 7, which does not contain the A-ring, showed efficacy with high selectivity indices for drug-resistant leukemias. On the other hand, substitutions on the D-ring of 4a for fluorine or iodine did not improve the antileukemic activity. In silico studies concerning Lipinskís rule of five, ADMET properties and drug scores of those compounds were performed, indicating good physicochemical properties for all compounds, in special for compound 7.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Tosyl Compounds / Pterocarpans / Antineoplastic Agents Type of study: Prognostic_studies / Risk_factors_studies Limits: Female / Humans Language: En Journal: Bioorg Chem Year: 2018 Document type: Article Affiliation country: Brazil Country of publication: United States

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Tosyl Compounds / Pterocarpans / Antineoplastic Agents Type of study: Prognostic_studies / Risk_factors_studies Limits: Female / Humans Language: En Journal: Bioorg Chem Year: 2018 Document type: Article Affiliation country: Brazil Country of publication: United States