Design, Synthesis, and Biological Evaluation of Novel Triazine‐Based Dual Histone Deacetylase/phosphatidylinositol 3‐kinase Inhibitors for Breast Cancer Therapy
values below 5 µM in MDA-MB-231 cells. Western blot analysis confirmed inhibition of HDAC and PI3K signaling in treated cells. Molecular docking and dynamics simulations further revealed stable binding modes and favorable interactions within the active sites of both targets. Overall, 5b and 5f represent promising lead candidates for further optimization toward the development of novel dual HDAC/PI3K inhibitors with potential application in TNBC therapy, as evaluated in TNBC-relevant models.
Authors
- Daniel Alencar Rodrigues (ORCID: https://orcid.org/0000-0001-7898-7093)
- Pedro de Sena Murteira Pinheiro (ORCID: https://orcid.org/0000-0003-4148-4243)
- D Vareslija
- Lara Luzietti (ORCID: https://orcid.org/0000-0002-5151-3979)
- Gustavo Salgado Pires
- Tríona Ní Chonghaile (ORCID: https://orcid.org/0000-0002-3041-4031)
- Ana Ryan (ORCID: https://orcid.org/0009-0006-9540-3567)
- Danilo Sarti
- Matthew Hiller
- Crisamie Regidor
Institutions
- Universidade Federal do Rio de Janeiro (BR)
- Royal College of Surgeons in Ireland (IE)
Publication Details
- Journal
- ChemMedChem
- Published
- 2026-04-25
- DOI
- https://doi.org/10.1002/cmdc.202501041
- Primary Topic
- Histone Deacetylase Inhibitors Research
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Breast Cancer Now
- Royal College of Surgeons in Ireland
- Irish Research Council for Science, Engineering and Technology
- Irish Research Council
- Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro
- Instituto Nacional de Ciência e Tecnologia de Fármacos e Medicamentos