Medicinal Chemistry Research

, Volume 28, Issue 1, pp 13–27 | Cite as

Synthesis, antimalarial, antiproliferative, and apoptotic activities of benzimidazole-5-carboxamide derivatives

  • Jesús A. Romero
  • María E. Acosta
  • Neira D. Gamboa
  • Michael R. Mijares
  • Juan B. De Sanctis
  • Ligia J. Llovera
  • Jaime E. CharrisEmail author
Original Research


Twenty-eight compounds of the type N´-substituted-2-(5-nitroheterocyclic-2-yl)-3H-benzo[d]imidazole-5-carboxamide were obtained using as an oxidizing agent the nitrobenzene to obtain the benzimidazole scaffold, a modification of the Steglich esterification reaction was used to obtain the final compounds. The compounds were tested as potential inhibitors of the β-hematin formation in vitro, and in vivo were tested as antimalarial against mice infected by a strain of Plasmodium berghei ANKA sensitive to chloroquine. The survival time was increased by the compounds 3a and 4d to 17.00 ± 1.26 and 20.20 ± 1.95 days, while the progress of the infection was reduced to 4.02 ± 0.45 and 3.05 ± 0.09, respectively. The cytotoxic activity of all these compounds was assessed against Jurkat E6.1 and HL60 two human cancer cell line, and fresh human lymphocytes. Four compounds 4a, n and 5a, n showed enhanced cytotoxicity against Jurkat E6.1 and HL60 cell lines; fresh lymphocytes were not affected. Using flow cytometry, apoptotic cell death was observed at 24 h. The aforementioned compounds enhanced apoptosis both tumor cell lines decreasing cell survival by inhibiting autophagy.


Benzimidazol Antimalarial P.berghei β-hematin Antiproliferative Apoptosis 



We thank the IIF and CDCH-UCV (grants IIF.02-2017, PG. 06-8627-2013/2) programs for financial support.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2018_2258_MOESM1_ESM.docx (22 kb)
Supplementary Information
44_2018_2258_MOESM2_ESM.docx (2.3 mb)
Supplementary Information


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© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Jesús A. Romero
    • 1
  • María E. Acosta
    • 1
  • Neira D. Gamboa
    • 1
  • Michael R. Mijares
    • 2
    • 3
  • Juan B. De Sanctis
    • 2
  • Ligia J. Llovera
    • 4
  • Jaime E. Charris
    • 1
    Email author return OK on get
  1. 1.Laboratorio de Síntesis Orgánica, Unidad de Bioquímica, Facultad de FarmaciaUniversidad Central de VenezuelaCaracasVenezuela
  2. 2.Instituto de inmunología, Facultad de MedicinaUniversidad Central de VenezuelaCaracasVenezuela
  3. 3.Unidad de Biotecnología, Facultad de FarmaciaUniversidad Central de VenezuelaCaracasVenezuela
  4. 4.Laboratorio de Resonancia Magnética Nuclear, Centro de QuímicaInstituto Venezolano de Investigaciones CientíficasCaracasVenezuela

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