Cytotoxicity and TOP1-targeting activity of 8- and 9-amino derivatives of 5-butyl- and 5-(2-N,N-dimethylamino)ethyl-5H-dibenzo[c,h][1,6]naphthyridin-6-ones.
Studies on substituted 5H-dibenzo[c,h][1,6]naphthyridin-6-ones and 6H-dibenzo[c,h][2,6]naphthyridin-5-ones have demonstrated that hydrophilic substituents at the 2-position of an ethyl group at the 5- and 6-positions, respectively, can enhance biological activity. The compatibility of such hydrophilic groups at other sites with either TOP1-targeting activity or potent cytotoxic activity has not been explored. The present study examines the influence on biological activity of either a 2-(N,N-dimethylamino)ethyl or a N,N-dimethylacetamide derivative of 8- or 9-amino-5H-dibenzo[c,h]naphthyridin-6-ones that have a 5-butyl- or 5-[2-(N,N-dimethylamino)ethyl]-substituent.
Sharma
Lisa
L
Department of Pharmaceutical Chemistry, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, NJ 08854-8020, USA.
Tsai
Yuan-Chin
YC
Liu
Angela A
AA
Liu
Leroy F
LF
LaVoie
Edmond J
EJ
D045744:Cell Line, Tumor; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D006801:Humans; D020128:Inhibitory Concentration 50; D009287:Naphthyridines / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity*
D009287:Naphthyridines; D004264:DNA Topoisomerases, Type I