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  3. New insights into 3-(aminomethyl)naphthoquinones: Evaluation of cytotoxicity, electrochemical behavior and search for structure-activity correlation

New insights into 3-(aminomethyl)naphthoquinones: Evaluation of cytotoxicity, electrochemical behavior and search for structure-activity correlation

  • Bioorg Med Chem Lett. 2016 Aug 1;26(15):3537-42. doi: 10.1016/j.bmcl.2016.06.027.
Gustavo B da Silva 1,  Amanda P Neves 2,  Maria D Vargas 3,  José D B Marinho-Filho 4,  Letícia V Costa-Lotufo 5
Affiliations

Affiliations

  • 1 Instituto de Química, Universidade Federal Fluminense, Campus do Valonguinho, Outeiro São João Batista s/n, Centro, Niterói, RJ 24020-150, Brazil. Electronic address: gustavobezerrads@gmail.com.
  • 2 Instituto de Química, Universidade Federal Fluminense, Campus do Valonguinho, Outeiro São João Batista s/n, Centro, Niterói, RJ 24020-150, Brazil; Departamento de Química, Universidade Federal Rural do Rio de Janeiro, Campus de Seropédica, BR-465 km 7, Seropédica, RJ 23890-000, Brazil.
  • 3 Instituto de Química, Universidade Federal Fluminense, Campus do Valonguinho, Outeiro São João Batista s/n, Centro, Niterói, RJ 24020-150, Brazil. Electronic address: mdvargas@vm.uff.br.
  • 4 Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal do Ceará, Rua Coronel Nunes de Mello 1127, Rodolfo Teófilo, Fortaleza, CE 60430-270, Brazil; Curso de medicina, Universidade Federal do Piauí-Campus Ministro Reis Velloso, Rua Capitão Claro, 382, Centro, Parnaíba, PI 64200-500, Brazil.
  • 5 Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal do Ceará, Rua Coronel Nunes de Mello 1127, Rodolfo Teófilo, Fortaleza, CE 60430-270, Brazil; Departamento de Farmacologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP 05508-900, Brazil.
PMID: 27363939 DOI: 10.1016/j.bmcl.2016.06.027
Abstract

Herein we describe the structure-activity relationship of a large library of Mannich Bases (MBs) synthesized from 2-hydroxy-1,4-naphthoquinone. In general, the compounds have shown high to moderate activity against the HL-60 (promyelocytic leukaemia) cell line with IC50=1.1-19.2μM. Our results suggest that the nature of the aryl moiety introduced in the structure of MBs by the aldehyde component is crucial to the cytotoxicity, and although the group originated from the primary amine has a lesser influence, aromatic ones were found to suppress the activity. Thus, MBs derived from salicylaldehydes or 2-pyridinecarboxaldehyde and aliphatic amines are the most active compounds. A satisfactory correlation of the EpIIc versus IC50 (μM) in dimethylsulfoxide was observed. The most cytotoxic MBs (Series a-c, derived from salicylaldehydes) showed the least negative EpIIc values. Noteworthy, however, Series d (derived from 2-pyridinecarboxaldehyde) did not follow this correlation. They exhibited both the lowest IC50 and the most negative EpIIc values, thus suggesting that Other factors also influence the cytotoxicity of the MBs, such as lipophilicity, electronic distribution and hydrogen bonding.

Keywords

Cyclic voltammetry; Cytotoxicity; Drug design; Mannich bases; Structure–activity relationship.

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