Transcription-inhibition and antitumor activities of N-alkylated tetraazacyclododecanes.
A series of alkyl-substituted tetraazacyclododecane congeners were synthesized, and their antitumor activities towards human HeLa cells as well as their effect on the in vitro transcription with T7 RNA polymerase were investigated. A structure-activity-relationship (SAR) study identified the most-active congeners as those with medium alkyl-chain lengths. Three compounds, 5-7, were found to exhibit significant biological activities, with IC50 values towards HeLa cells in the low-micromolar range.
Xiong
Xiao-Qin
XQ
College of Chemistry & Molecular Sciences, Wuhan University, Wuhan, Hubei 430072, PR China.
Liang
Feng
F
Yang
Li
L
Wang
Xiao-Lin
XL
Zhou
Xiang
X
Zheng
Cong-Yi
CY
Cao
Xiao-Ping
XP
D000478:Alkylation / Q000187:drug effects; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001372:Aza Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006367:HeLa Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009369:Neoplasms / Q000235:genetics / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship; D014158:Transcription, Genetic / Q000187:drug effects*
D000970:Antineoplastic Agents; D001372:Aza Compounds; D012333:RNA, Messenger