Synthesis and Quantitative Structure–Activity Relationship of Imidazotetrazine Prodrugs with Activity Independent of O6‑Methylguanine-DNA-methyltransferase, DNA Mismatch Repair, and p53

• Published in: Journal of medicinal chemistry Vol. 56; no. 17; pp. 7120 - 7132
• Main Authors: Pletsas, Dimitrios, Garelnabi, Elrashied A. E, Li, Li, Phillips, Roger M, Wheelhouse, Richard T
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 12.09.2013; Amer Chemical Soc
• Subjects: Base Pair Mismatch; Chemistry, Medicinal; DNA Repair; Life Sciences & Biomedicine; O-Methylguanine-DNA Methyltransferase - chemistry; Pharmacology & Pharmacy; Prodrugs - chemistry; Quantitative Structure-Activity Relationship; Science & Technology; Tumor Suppressor Protein p53 - metabolism; THERAPY-RELATED CANCER; ANTITUMOR DRUG TEMOZOLOMIDE; IN-VITRO; METHYLATING AGENTS; METHYLTRANSFERASE; MECHANISM; DISCOVERY SCREEN; DECOMPOSITION; ALKYLTRANSFERASE; MITOZOLOMIDE

The antitumor prodrug temozolomide is compromised by its dependence for activity on DNA mismatch repair (MMR) and the repair of the chemosensitive DNA lesion, O6-methylguanine (O6-MeG), by O6-methylguanine-DNA-methyltransferase (E.C. 2.1.1.63, MGMT). Tumor response is also dependent on wild-type p53...