Targeting gliomas with triazene-based hybrids: Structure-activity relationship, mechanistic study and stability.

Abstract

Herein we report novel hybrid compounds based on valproic acid and DNA-alkylating triazene moieties, 1, with therapeutic potential for glioblastoma multiforme chemotherapy. We identified hybrid compounds 1d and 1e to be remarkably more potent against glioma and more efficient in decreasing invasive cell properties than temozolomide and endowed with chemical and plasma stability. In contrast to temozolomide, which undergoes hydrolysis to release an alkylating metabolite, the valproate hybrids showed a low potential to alkylate DNA. Key physicochemical properties align for optimal CNS penetration, highlighting the potential of these effective triazene based-hybrids for enhanced anticancer chemotherapy.

• Authors: Cláudia Braga, Ana R Vaz, M Conceição Oliveira, M Matilde Marques, Rui Moreira, Dora Brites, Maria J Perry
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 172 Pg. 16-25 (Jun 15 2019) ISSN: 1768-3254 [Electronic] France
• PMID: 30939350 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents
• Triazenes

Topics

• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Brain Neoplasms (drug therapy, pathology)
• Cell Movement (drug effects)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Glioma (drug therapy, pathology)
• Humans
• Molecular Structure
• Structure-Activity Relationship
• Triazenes (chemical synthesis, chemistry, pharmacology)
• Tumor Cells, Cultured