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Synthesis and Biological Evaluation of Potential Oncoimmunomodulator Agents

Fourteen triazole-scaffold derivatives were synthetized and biologically evaluated as potential oncoimmunomodultator agents by targeting both PD-L1 and c-Myc. First, the antiproliferative activity of these molecules on the monocultures of several tumor cell lines (HT-29, A-549, and MCF-7) and on the...

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Autores principales: Gil-Edo, Raquel, Espejo, Sara, Falomir, Eva, Carda, Miguel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917184/
https://www.ncbi.nlm.nih.gov/pubmed/36768935
http://dx.doi.org/10.3390/ijms24032614
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author Gil-Edo, Raquel
Espejo, Sara
Falomir, Eva
Carda, Miguel
author_facet Gil-Edo, Raquel
Espejo, Sara
Falomir, Eva
Carda, Miguel
author_sort Gil-Edo, Raquel
collection PubMed
description Fourteen triazole-scaffold derivatives were synthetized and biologically evaluated as potential oncoimmunomodultator agents by targeting both PD-L1 and c-Myc. First, the antiproliferative activity of these molecules on the monocultures of several tumor cell lines (HT-29, A-549, and MCF-7) and on the non-tumor cell line HEK-293 was studied. Then, the effects on the mentioned biological targets were also evaluated. Finally, the effect on cancer cell viability when the molecules were co-cultured with immune cells (Jurkat T cells or THP-1) was also determined. Compounds bearing a bromoophenyl group were selected because of their excellent results, and their effect on IL-6 secretion was also studied. In conclusion, we found compounds that are capable of downregulating c-Myc, as well as influencing and altering the distribution of PD-L1 in tumor cells; the compounds are thus capable of influencing the behavior of defensive cells towards cancer cells. p-Bromophenyltriazol 3 is the most active of these as a PD-L1 and c-Myc downregulator and as a potential immunomodulator agent. Moreover, it exhibits an interesting action on inflammation-related cytokine IL-6.
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spelling pubmed-99171842023-02-11 Synthesis and Biological Evaluation of Potential Oncoimmunomodulator Agents Gil-Edo, Raquel Espejo, Sara Falomir, Eva Carda, Miguel Int J Mol Sci Article Fourteen triazole-scaffold derivatives were synthetized and biologically evaluated as potential oncoimmunomodultator agents by targeting both PD-L1 and c-Myc. First, the antiproliferative activity of these molecules on the monocultures of several tumor cell lines (HT-29, A-549, and MCF-7) and on the non-tumor cell line HEK-293 was studied. Then, the effects on the mentioned biological targets were also evaluated. Finally, the effect on cancer cell viability when the molecules were co-cultured with immune cells (Jurkat T cells or THP-1) was also determined. Compounds bearing a bromoophenyl group were selected because of their excellent results, and their effect on IL-6 secretion was also studied. In conclusion, we found compounds that are capable of downregulating c-Myc, as well as influencing and altering the distribution of PD-L1 in tumor cells; the compounds are thus capable of influencing the behavior of defensive cells towards cancer cells. p-Bromophenyltriazol 3 is the most active of these as a PD-L1 and c-Myc downregulator and as a potential immunomodulator agent. Moreover, it exhibits an interesting action on inflammation-related cytokine IL-6. MDPI 2023-01-30 /pmc/articles/PMC9917184/ /pubmed/36768935 http://dx.doi.org/10.3390/ijms24032614 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gil-Edo, Raquel
Espejo, Sara
Falomir, Eva
Carda, Miguel
Synthesis and Biological Evaluation of Potential Oncoimmunomodulator Agents
title Synthesis and Biological Evaluation of Potential Oncoimmunomodulator Agents
title_full Synthesis and Biological Evaluation of Potential Oncoimmunomodulator Agents
title_fullStr Synthesis and Biological Evaluation of Potential Oncoimmunomodulator Agents
title_full_unstemmed Synthesis and Biological Evaluation of Potential Oncoimmunomodulator Agents
title_short Synthesis and Biological Evaluation of Potential Oncoimmunomodulator Agents
title_sort synthesis and biological evaluation of potential oncoimmunomodulator agents
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9917184/
https://www.ncbi.nlm.nih.gov/pubmed/36768935
http://dx.doi.org/10.3390/ijms24032614
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