Synthesis and Biological Evaluation of New 3,4-diarylmaleimides as Enhancers (modulators) of Doxorubicin Cytotoxic Activity on Cultured Tumor Cells from a Real Case of Breast Cancer

  • Jessica R. Gutierrez-Cano Universidad de Guanajuato
  • Pradip D. Nahide Universidad de Guanajuato
  • Velayudham Ramadoss Universidad de Guanajuato
  • Yuvraj Satkar Universidad de Guanajuato
  • Rafael Ortiz-Alvarado Universidad Michoacana de San Nicolás de Hidalgo
  • Clara Alba-Betancourt Universidad de Guanajuato
  • Claudia L. Mendoza-Macías Universidad de Guanajuato
  • César R. Solorio-Alvarado Universidad de Guanajuato
Keywords: Breast cancer, Maleimide, Doxorubicin, synergistic cancer treatment

Abstract

A series of new 3,4-diarylmaleimides were synthesized in an optimized and efficient lineal sequence of three steps, starting from commercial maleimide. The biological evaluation of these compounds as enhancers (activity modulators) in the co-administration with doxorubicin treatment in breast cancer cells directly obtained from a patient, were essayed. The cancerous tissue BT026-512N was provided by the National Institute of Cancerology (INCAN) of México. This tissue was obtained by biopsy from a patient diagnosed with stage IIB ductal breast cancer. The results obtained in the assays, show decreased cell viability on the cultured cells for all of the maleimides synthesized in combinatorial administration with doxorubicin. The highest mortality effect was determined for maleimides 9 and 29 increased in close to three times the effect compared with treatment using only doxorubicin. Based on previous functionalized maleimides core reports and Molinspiration chemoinformatic analysis, these results could possibly point out to the Pg-p glycoprotein as bio-molecular action target of maleimides by kinase phosphorylation-inhibition, although more experimental data is necessary.

Author Biographies

Jessica R. Gutierrez-Cano, Universidad de Guanajuato
Departamento de Química, División de Ciencias Naturales y Exactas, Campus Guanajuato
Pradip D. Nahide, Universidad de Guanajuato
Departamento de Química, División de Ciencias Naturales y Exactas, Campus Guanajuato
Velayudham Ramadoss, Universidad de Guanajuato
Departamento de Química, División de Ciencias Naturales y Exactas, Campus Guanajuato
Yuvraj Satkar, Universidad de Guanajuato
Departamento de Química, División de Ciencias Naturales y Exactas, Campus Guanajuato
Rafael Ortiz-Alvarado, Universidad Michoacana de San Nicolás de Hidalgo
Facultad de Químico Farmacobiología
Clara Alba-Betancourt, Universidad de Guanajuato
Departamento de Farmacia, División de Ciencias Naturales y Exactas, Campus Guanajuato
Claudia L. Mendoza-Macías, Universidad de Guanajuato
Departamento de Farmacia, División de Ciencias Naturales y Exactas, Campus Guanajuato
César R. Solorio-Alvarado, Universidad de Guanajuato
Departamento de Farmacia, División de Ciencias Naturales y Exactas, Campus Guanajuato
Published
10-12-2017