Oxoisoaporphine alkaloid derivatives: synthesis, DNA binding affinity and cytotoxicity.
A series of novel oxoisoaporphine alkaloid derivatives, 9-aminoalkanamido-1-azabenzanthrone (general formula Ar-NHCO(CH(2))(n)NR(2), Ar=1-azabenzanthrone, n=1, 2 or 3), had been synthesized. Compared with 1-azabenzanthrone, the derivatives had significantly higher DNA binding affinity with calf thymus DNA, and higher potent cytotoxicity against different tumor cell lines. The cytotoxicity and the structure-activity relationship of the prepared compounds were studied. The derivatives with two methylene groups (n=2), and piperidine or ethanolamine functional group in the side chain exhibited highest DNA binding affinity and cytotoxicity.
Tang
Huang
H
School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China.
Wang
Xiao-Dong
XD
Wei
Yong-Biao
YB
Huang
Shi-Liang
SL
Huang
Zhi-Shu
ZS
Tan
Jia-Heng
JH
An
Lin-Kun
LK
Wu
Jian-Yong
JY
Chan
Albert Sun-Chi
AS
Gu
Lian-Quan
LQ
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001060:Aporphines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004247:DNA / Q000737:chemistry*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D051379:Mice; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001060:Aporphines; D004247:DNA