Hypoxia activated prodrugs of a 9-aza-anthrapyrazole derivative that has promising anticancer activity.
Mono- and bis-N-oxides of a 9-aza-anthrapyrazole derivative having two 2-(dimethylamino)ethyl appendages were prepared by using a mild oxaziridine reagent. Biochemical and cell culture assays indicate that the bis-oxide is an inactive prodrug that readily converts to the active parent molecule under hypoxic conditions that are analogous to those present within certain tumors.
Center for Drug Design and Development, College of Pharmacy and Pharmaceutical Sciences, The University of Toledo, Toledo, Ohio 43606, United States.
Mohammad H
MH
El-Dakdouki
Nicholas
N
Adamski
Lecia
L
Foster
Miles P
MP
Hacker
Paul W
PW
Erhardt
D000880:Anthraquinones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D005609:Free Radicals / Q000378:metabolism; D006801:Humans; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000880:Anthraquinones; D000970:Antineoplastic Agents; D001372:Aza Compounds; D005609:Free Radicals; D011355:Prodrugs; D011720:Pyrazoles