Cyclopropyl indolequinones: mechanistic probes for bioreductive anticancer drug action.
A series of cyclopropyl indolequinones based on structures 5-7 was designed and synthesized to probe the structural features essential for bioreductive cytotoxicity. Ring opening of the cyclopropane ring under radical conditions was demonstrated to be mechanistically feasible, and related to the involvement of such one-electron processes in the cytotoxicity of cyclopropyl indolequinones under hypoxic conditions.
Moody
C J
CJ
Department of Chemistry, Loughborough University, Leicestershire, UK.
Norton
C L
CL
Slawin
A M
AM
Taylor
S
S
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D016923:Cell Death; D015687:Cell Hypoxia; D002460:Cell Line; D006224:Cricetinae; D018360:Crystallography, X-Ray; D003521:Cyclopropanes / Q000138:chemical synthesis*; D007211:Indoles / Q000138:chemical synthesis*; D016685:Mitomycin / Q000737:chemistry / Q000494:pharmacology; D008937:Mitomycins; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011355:Prodrugs; D011809:Quinones / Q000138:chemical synthesis*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D003521:Cyclopropanes; D007211:Indoles; D008937:Mitomycins; D011355:Prodrugs; D011809:Quinones; D016685:Mitomycin