Evaluation of Novel Imidazotetrazine Analogues Designed to Overcome Temozolomide Resistance and Glioblastoma Regrowth

• Published in: Molecular cancer therapeutics Vol. 14; no. 1; pp. 111 - 119
• Main Authors: Ramirez, Yulian P., Mladek, Ann C., Phillips, Roger M., Gynther, Mikko, Rautio, Jarkko, Ross, Alonzo H., Wheelhouse, Richard T., Sakaria, Jann N.
• Format: Journal Article
• Language: English
• Published: United States 01.01.2015
• Subjects: Aniline Compounds - administration & dosage; Aniline Compounds - chemical synthesis; Aniline Compounds - pharmacokinetics; Animals; Antineoplastic Agents, Alkylating - administration & dosage; Antineoplastic Agents, Alkylating - chemical synthesis; Antineoplastic Agents, Alkylating - pharmacokinetics; Ataxia Telangiectasia Mutated Proteins - metabolism; Brain Neoplasms - drug therapy; Brain Neoplasms - metabolism; Cell Cycle - drug effects; Cell Line, Tumor; Dacarbazine - administration & dosage; Dacarbazine - analogs & derivatives; Dacarbazine - pharmacokinetics; DNA Damage - drug effects; DNA Modification Methylases - metabolism; DNA Repair Enzymes - metabolism; Drug Resistance, Neoplasm - drug effects; Fanconi Anemia Complementation Group D2 Protein - metabolism; Gene Expression Regulation, Neoplastic - drug effects; Glioblastoma - drug therapy; Glioblastoma - metabolism; Heterocyclic Compounds, 2-Ring - administration & dosage; Heterocyclic Compounds, 2-Ring - chemical synthesis; Heterocyclic Compounds, 2-Ring - pharmacokinetics; Humans; Mice; Mice, Inbred C57BL; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - metabolism; Temozolomide; Tumor Suppressor Proteins - metabolism; Xenograft Model Antitumor Assays

The cellular responses to two new temozolomide (TMZ) analogues, DP68 and DP86, acting against glioblastoma multiforme (GBM) cell lines and primary culture models are reported. Dose–response analysis of cultured GBM cells revealed that DP68 is more potent than DP86 and TMZ and that DP68 was effective...