2. Academic Validation
  3. A Schmidt rearrangement-mediated synthesis of novel tetrahydro-benzo[1,4]diazepin-5-ones as potential anticancer and antiprotozoal agents

A Schmidt rearrangement-mediated synthesis of novel tetrahydro-benzo[1,4]diazepin-5-ones as potential anticancer and antiprotozoal agents

  • Eur J Med Chem. 2017 Dec 1:141:567-583. doi: 10.1016/j.ejmech.2017.10.024.
Daniel Insuasty 1,  Sara M Robledo 2,  Iván D Vélez 2,  Paola Cuervo 3,  Braulio Insuasty 1,  Jairo Quiroga 1,  Manuel Nogueras 4,  Justo Cobo 4,  Rodrigo Abonia 5
Affiliations

Affiliations

  • 1 Research Group of Heterocyclic Compounds, Department of Chemistry, Universidad del Valle, A. A. 25360 Cali, Colombia.
  • 2 PECET, Instituto de Investigaciones Médicas, Facultad de Medicina, Universidad de Antioquia, PO Box 1226, Medellín, Colombia.
  • 3 Group of Studies in Synthesis and Applications of Heterocyclic Compounds, Department of Chemistry, Universidad Nacional de Colombia, Colombia.
  • 4 Department of Inorganic and Organic Chemistry, Universidad de Jaén, 23071 Jaén, Spain.
  • 5 Research Group of Heterocyclic Compounds, Department of Chemistry, Universidad del Valle, A. A. 25360 Cali, Colombia. Electronic address: rodrigo.abonia@correounivalle.edu.co.
PMID: 29102177 DOI: 10.1016/j.ejmech.2017.10.024
Abstract

Novel tetrahydro-5H-benzo[e][1,4]diazepin-5-ones, several of them, containing the quinoline pharmacophore, were synthesized via a Schmidt rearrangement from their corresponding 1,2,3,4-tetrahydro-4-quinolones mediated by the NaN3/H2SO4 reaction conditions. Twelve of the obtained compounds were in vitro screened by the US National Cancer Institute (NCI) for their ability to inhibit 60 different human tumor cell lines, where compound 24a presented a remarkable activity against 58 of the 60 Cancer cell lines, with the most important GI50 values ranging from 0.047 to 8.16 μM and LC50 values ranging from 9.4 to > 100 μM. Additionally, some of them were evaluated as antimalarial, antitrypanosomal and antileishmanial agents. The best antimalarial response was observed for compound 22g with an EC50 = 13.61 μg/mL for Plasmodium falciparum, while compound 24d exhibited high activity against Trypanosoma cruzi. and Leishmania (V) panamensis with EC50 = 2.78 μg/mL and 3.35 μg/mL respectively.

Keywords

Anticancer activity; Antiprotozoal activity; Benzo[1,4]diazepin-5-ones; Chalcones; Quinolines; Schmidt rearrangement.

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