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Targeting gliomas with triazene-based hybrids: Structure-activity relationship, mechanistic study and stability
- Source :
- European journal of medicinal chemistry. 172
- Publication Year :
- 2019
-
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.
- Subjects :
- Cell Survival
Metabolite
medicine.medical_treatment
Cell
Antineoplastic Agents
01 natural sciences
03 medical and health sciences
chemistry.chemical_compound
Structure-Activity Relationship
Cell Movement
Glioma
Drug Discovery
medicine
Tumor Cells, Cultured
Structure–activity relationship
Humans
Triazene
030304 developmental biology
Cell Proliferation
Pharmacology
0303 health sciences
Chemotherapy
Temozolomide
Dose-Response Relationship, Drug
Molecular Structure
010405 organic chemistry
Chemistry
Brain Neoplasms
Organic Chemistry
General Medicine
medicine.disease
0104 chemical sciences
medicine.anatomical_structure
Cancer research
Drug Screening Assays, Antitumor
Triazenes
DNA
medicine.drug
Subjects
Details
- ISSN :
- 17683254
- Volume :
- 172
- Database :
- OpenAIRE
- Journal :
- European journal of medicinal chemistry
- Accession number :
- edsair.doi.dedup.....0b532c962c109fb152f940a50fa2784b