3,4-Dihydro-1H-[1,3]oxazino[4,5-c]acridines as a new family of cytotoxic drugs.
A series of [1,3]oxazino fused acridines has been prepared as precursors of cytotoxic 3-amino-4-hydroxymethylacridine 2. Their cytotoxic activity has been evaluated against HT29 colon carcinoma cell line and was shown to be dependent on the nature of the substituent located on position 2 of the oxazine ring. Additionally, the nitrophenyl derivative 3f is activated by nitroreductase, indicating its potency as prodrug for either gene-directed or antibody-directed enzyme prodrug therapies.
Ouberai
Myriam
M
LEDSS, CNRS UMR 5616 & ICMG-FR260, Université Joseph Fourier, BP53, Grenoble, France.
Asche
Christian
C
Carrez
Danièle
D
Croisy
Alain
A
Dumy
Pascal
P
Demeunynck
Martine
M
D000166:Acridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000145:classification / Q000633:toxicity*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D006859:Hydrogen / Q000737:chemistry*; D015394:Molecular Structure; D010078:Oxazines / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000166:Acridines; D000970:Antineoplastic Agents; D010078:Oxazines; D006859:Hydrogen