Synthesis of a netropsin conjugate of a water-soluble epi-quinocarcin analogue: the importance of stereochemistry at nitrogen.
The efficient synthesis of a water-soluble C11a-epi-analogue (6b) of quinocarcin is described. This substance, and a netropsin amide conjugate (8) lack the capacity to inflict oxidative damage on DNA due to the stereoelectronic geometry of their oxazolidine nitrogen atoms. The capacity of these substances to alkylate DNA through the generation of an iminium species has been examined. Both compounds were found to be unreactive as DNA alkylating agents. The results of this study are discussed in the context of previous proposals on the mode of action of this family of antitumor alkaloids.
Herberich
B
B
Department of Chemistry, Colorado State University, Fort Collins 80523, USA.
Scott
J D
JD
Williams
R M
RM
D000477:Alkylating Agents / Q000737:chemistry / Q000378:metabolism; D000478:Alkylation; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000378:metabolism; D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry / Q000378:metabolism; D000998:Antiviral Agents / Q000737:chemistry / Q000378:metabolism; D007202:Indicators and Reagents; D007546:Isoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D009429:Netropsin / Q000138:chemical synthesis* / Q000737:chemistry* / Q000378:metabolism; D009580:Nitroblue Tetrazolium; D009838:Oligodeoxyribonucleotides / Q000378:metabolism; D012995:Solubility; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013481:Superoxides / Q000378:metabolism
D000477:Alkylating Agents; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D018906:Antineoplastic Agents, Alkylating; D000998:Antiviral Agents; D007202:Indicators and Reagents; D007546:Isoquinolines; D009838:Oligodeoxyribonucleotides; D013481:Superoxides; D009580:Nitroblue Tetrazolium; D009429:Netropsin; C038710:quinocarcin