Synthesis, docking, machine learning and antiproliferative activity of the 6-ferrocene/heterocycle-2-aminopyrimidine and 5-ferrocene-1H-Pyrazole derivatives obtained by microwave-assisted Atwal reaction as potential anticancer agents.

Journal: Bioorganic & medicinal chemistry letters
PMID:

Abstract

A simple and fast methodology under microwave irradiation for the synthesis of 2-aminopyrimidine and pyrazole derivatives using Atwal reaction is reported. After the optimization of the reaction conditions, eight 2-aminolpyrimidines containing ferrocene and heterocycles and three ferrocene pyrazoles were synthesized from the respective chalcones in good yields. Eight compounds had their structure determined by X-ray diffraction. The molecular hybrid 6a-h and 9a-c were tested on four cancer cell lines - HCT116, PC3, HL60 and SNB19 - where four pyrimidine 6a, 6f-h and one pyrazole 9c derivatives show promising antiproliferative activity. In addition, docking simulation and machine learning methods were carried out to explain the biological activity achieved by the synthetized compounds.

Authors

  • Eclair Venturini Filho
    Chemistry Department, Federal University of Espírito Santo, Vitória, Espírito Santo CEP.:29075-910, Brazil.
  • Jorge W S Pina
    Chemistry Department, Federal University of Espírito Santo, Vitória, Espírito Santo CEP.:29075-910, Brazil.
  • Mariana K Antoniazi
    Chemistry Department, Federal University of Espírito Santo, Vitória, Espírito Santo CEP.:29075-910, Brazil.
  • Laiza B Loureiro
    Chemistry Department, Federal University of Espírito Santo, Vitória, Espírito Santo CEP.:29075-910, Brazil.
  • Marcos A Ribeiro
    Chemistry Department, Federal University of Espírito Santo, Vitória, Espírito Santo CEP.:29075-910, Brazil.
  • Carlos B Pinheiro
    Physical Department, Minas Gerais Federal University, Av. Antônio Carlos 6627, Pampulha, Belo Horizonte, Minas Gerais CEP.: 30161-970 Brazil.
  • Celina J Guimarães
    Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará., Fortaleza, Ceará CEP 60430-275, Brazil; Pharmacy Sector, Foundation of Oncology Control of the State of Amazonas, Manaus, Amazonas, CEP 69040-010, Brazil.
  • Fátima C E de Oliveira
    Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará., Fortaleza, Ceará CEP 60430-275, Brazil.
  • Claudia Pessoa
    Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará., Fortaleza, Ceará CEP 60430-275, Brazil.
  • Alex G Taranto
    Laboratory of Drug Design and Bioinformatics, Federal University of São João del-Rei, São João del-Rei, Minas Gerais CEP: 36307-352, Brazil.
  • Sandro J Greco
    Chemistry Department, Federal University of Espírito Santo, Vitória, Espírito Santo CEP.:29075-910, Brazil. Electronic address: sandro.greco@ufes.br.