Synthesis and evaluation of piperazine and homopiperazine analogues of JS-K, an anti-cancer lead compound.
Here we report a number of novel JS-K structural analogues with sub-micromolar anti-proliferative activities against human leukemia cell lines HL-60 and U937; JS-K is the anti-cancer lead compound O(2)-(2,4-dinitrophenyl) 1-[(4-ethoxycarbonyl)piperazin-1-yl]diazen-1-ium-1,2-diolate. The ability of these compounds to generate intracellular nitric oxide correlated well with their observed anti-proliferative effects: analogues that had potent inhibitory activity against leukemia cells formed elevated levels of intracellular nitric oxide.
Chemistry Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, MD 21702, USA.
Rahul S
RS
Nandurdikar
Anna E
AE
Maciag
Michael L
ML
Citro
Paul J
PJ
Shami
Larry K
LK
Keefer
Joseph E
JE
Saavedra
Harinath
H
Chakrapani
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001391:Azo Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D006801:Humans; D009569:Nitric Oxide / Q000378:metabolism; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
D000970:Antineoplastic Agents; D001391:Azo Compounds; C474958:O(2)-(2,4-dinitrophenyl) 1-((4-ethoxycarbonyl)piperazin-1-yl)diazen-1-ium-1,2-diolate; D010879:Piperazines; D009569:Nitric Oxide