Development of novel oxygen-independent photosensitizers.
We proposed a strategy of photooxidizer-reduction activated alkylator (P-A) hybrid molecule to develop novel oxygen-independent photosensitizers. Two prototypes of such photosensitizers camptothecin-indolequinone (CPT-IQ) and camptothecin-nitrofuryl (CPT-NF) was designed and prepared. A mechanism of photo-induced oxidation and alkylation of 2'-deoxyguanosine by CPT-IQ was investigated. CPT-NF was confirmed to effectively induce DNA cleavage via 365-nm UV irradiation both under normaxia and hypoxia.
Zhang
Zhouen
Z
Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan. zhouen@astem.or,jp
Haruna
Ken-Ichi
K
Ito
Takeo
T
Hatta
Hiroshi
H
Nishimoto
Sei-Ichi
S
D000478:Alkylation; D000693:Anaerobiosis; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000528:radiation effects; D003849:Deoxyguanosine / Q000737:chemistry; D005663:Furans / Q000138:chemical synthesis / Q000737:chemistry* / Q000528:radiation effects; D010084:Oxidation-Reduction; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000528:radiation effects; D011809:Quinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000528:radiation effects; D014466:Ultraviolet Rays
C528367:4-deshydroxy-4-(N-methyl-(2-(((5-methoxy-1,2-dimethyl-4,7-dioxoindol-3-yl)methoxycarbonyl)(methyl)amino)ethyl)carbamoylmethyl)camptothecin; C528368:4-deshydroxy-4-(N-methyl-(2-(((5-nitrofur-2-yl)methoxycarbonyl)(methyl)amino)ethyl)carbamoylmethyl)camptothecin; D005663:Furans; D017319:Photosensitizing Agents; D011809:Quinones; D003849:Deoxyguanosine; D002166:Camptothecin