Amino- and glycoconjugates of pyrido[4,3,2-kl]acridine. Synthesis, antitumor activity, and DNA binding.
A series of amino- and glycoconjugates of pyrido[4,3,2-kl]acridine and pyrido[4,3,2-kl]acridin-4-one have been prepared. The most active molecules, the amino conjugates 7 and 11, display a cytostatic activity against HT-29 cancer cells at micromolar concentration. This activity correlates well with a strong DNA binding. The molecules, amino or glycoconjugates, bind DNA by intercalation, the amino or glyco substituent being located in one groove. None of the molecules inhibits topoisomerase activity.
Bouffier
Laurent
L
LEDSS UMR5616 & ICMG-FR2607, Université Joseph Fourier, BP53, 38041 Grenoble cedex 9, France.
Baldeyrou
Brigitte
B
Hildebrand
Marie-Paule
MP
Lansiaux
Amélie
A
David-Cordonnier
Marie-Hélène
MH
Carrez
Danièle
D
Croisy
Alain
A
Renaudet
Olivier
O
Dumy
Pascal
P
Demeunynck
Martine
M
D000166:Acridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000586:Amination; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002942:Circular Dichroism; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D018983:DNA Footprinting; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D003850:Deoxyribonuclease I / Q000378:metabolism; D006031:Glycosylation; D019073:HT29 Cells; D006801:Humans; D015394:Molecular Structure; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D044366:Transition Temperature
D000166:Acridines; D000970:Antineoplastic Agents; D011725:Pyridines; D004247:DNA; D003850:Deoxyribonuclease I; D004264:DNA Topoisomerases, Type I