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.
Nandurdikar
Rahul S
RS
Chemistry Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute at Frederick, MD 21702, USA.
Maciag
Anna E
AE
Citro
Michael L
ML
Shami
Paul J
PJ
Keefer
Larry K
LK
Saavedra
Joseph E
JE
Chakrapani
Harinath
H
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