Design, synthesis, and in vitro evaluation of a carbamazepine derivative with antitumor potential in a model of Acute Lymphoblastic Leukemia

Autores organización

• 

  James Oswaldo Guevara Pulido

  Autor

Autores

• Álvarez-Gómez C.
• Fonseca-Benítez A.V.

Unidades de investigación

• Investigación en Química Aplicada INQA

  

  Investigador

  James Oswaldo Guevara Pulido

Resumen

Acute lymphoblastic leukemia (ALL) is a significant concern in both pediatric and adult demographics. Despite 156 approved cancer therapies based on small molecules, a mere five apply to all types of leukemia. Unfortunately, adherence to these treatments is low due to adverse side effects. Consequently, there is an urgent need to identify more effective treatment options for ALL. This study presents a potential solution. We have designed over fifty analogs of carbamazepine, utilizing a combination of ligand-based and structure-based drug design methodologies. Among these analogs, we identified the CR80 analog, which demonstrated predicted binding values of -8.66 kcal/mol against beta-tubulin, a favorable LogP, and IC50 values suitable for in vitro evaluation. The CR80 compound was synthesized with a yield of 50% and subsequently assessed in vitro against the U-937 cell line. It obtained an IC50 value of 0.8 micromolar to 1 micromolar and a selectivity index of two, thus marking it as a promising candidate for in vivo studies. © 2025 Álvarez-Gómez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Keywords

• Antineoplastic Agents; Carbamazepine; Cell Line, Tumor; Cell Proliferation; Drug Design; Drug Screening Assays, Antitumor; Humans; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Tubulin; beta tubulin; carbamazepine; paclitaxel; antineoplastic agent; carbamazepine; tubulin; acute lymphoblastic leukemia; antineoplastic activity; Article; artificial neural network; carbon nuclear magnetic resonance; chromatography; controlled study; crystal structure; cytotoxicity; design; electrospray; Fourier transform infrared spectroscopy; high performance liquid chromatography; human; human cell; IC50; in vitro study; mass spectrometry; proton nuclear magnetic resonance; synthesis; thin layer chromatography; U-937 cell line; ultraviolet irradiation; B cell acute lymphoblastic leukemia; cell proliferation; chemistry; drug design; drug effect; drug screening; drug therapy; metabolism; pathology; synthesis; tumor cell line