Synthesis and bioevaluation of N-(arylalkyl)-homospermidine conjugates.
N1-(Arylalkyl)homospermidines (1c-1f) and terminally piperazine-substituted homospermidine conjugates (2a-2e) were synthesized and evaluated for cytotoxicity in mouse leukemia L1210, alpha-difluoromethylornithine (DFMO)-treated L1210, melanoma B16, spermidine (SPD)-treated B16, and HeLa cell lines. Results demonstrated that homospermidine was a more effective vector than piperazine-substituted homospermidine in ferrying diverse arenes into cells via the polyamine transporter. The leading compound, 9-anthracenemethyl-homospermidine (1a), was shown to induce apoptosis in B16 cells and IL-3 dependent FL5.12A pro-B cells. The novel conjugate 4-biphenylmethyl-homospermidine (1e) could also induce apoptosis. However, it exhibited different effect on the cell cycle of B16 cells compared to 1a.
Xie
Songqiang
S
Institute of Natural Products & Medicinal Chemistry, Henan University, Henan, Kaifeng 475001, China.
Cheng
Pengfei
P
Liu
Guangchao
G
Ma
Yuangfang
Y
Zhao
Jin
J
Chehtane
Mounir
M
Khaled
Annette R
AR
Phanstiel
Otto
O
Wang
Chaojie
C
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007377:Interleukin-3 / Q000494:pharmacology; D051379:Mice; D015394:Molecular Structure; D013095:Spermidine / Q000031:analogs & derivatives* / Q000737:chemistry*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D007377:Interleukin-3; D013095:Spermidine