The synthesis and molecular recognization of the polyamine transporter of hydrazine-modified diamine conjugates

A series of four novel hydrazine-modified diamine conjugates （7a-b, 8a-b） were synthesized and evaluated for cytotoxicity against Melanoma B 16, α-difluoromethylornithine （DFMO）-treated B 16, spermidine （SPD）-treated B 16, Mouse leukemia L 1210 and Hela cell lines. Both the DFMO-B 16 and SPD-B 16 experiments indicated that conjugates 7a-b and 8a-b could recognize the polyamine transporter （PAT） and enter the cells in part or in whole via PAT, although they were not as efficient as the reference, 9- anthracenemethyl homospermidine （1）. 2007 Chao Jie Wang. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.

Relationship between ATPase activity and conjugated polyamines in mito-chondrial membrane from wheat seedling roots under osmotic stress

The effects of osmotic stress on the ATPase activity, the contents of —SH group and conjugated polyamines in mitochondrial membrane from wheat seedling [Triticum aestivum L. cv. Yumai No.18(drought-tolerant) and cv. Yumai No.9(drought-sensitive)] roots were investigated. The results showed that ATPase activity and —SH group content decreased with polyethylene glycol(PEG) 6000(-0.55 MPa) treatment for 7 d, in concert with the decrease of the ratio of noncovalently conjugated spermidine(NCC-Spd)/noncovalently conjugated putrescine(NCC-Put) and increase of the covalently conjugated putrescine(CC-Put). Osmotic stress injury to Yangmai No.9 seedlings was alleviated greatly with 1 mmol/L exogenous spermidine(Spd), in concert with marked increases of the ratio of NCC-Spd/NCC-Put, —SH group contents and ATPase activity in mitochondrial membrane. Under osmotic stress, the concomitant treatment of Yumai No.18 seedlings with methylglyoxyl bis(guanylhydrazone) (MGBG), an inhibitor of S-adenosyl methionine decarboxylase(SAMDC), and phenanthrolin (o-Phen), an inhibitor of transglutaminase(TGase), caused a significant decrease of the ratio of NCC-Spd / NCC-Put, CC-Put contents, respectively, in concert with the marked decreases of ATPase activity, —SH group content and its tolerance to osmotic stress. All the results above suggested that osmotic stress tolerance of wheat seedlings was associated with the ATPase activity, the contents of —SH group, NCC-Spd and CC-Put in mitochondrial membrane.

The synthesis and bioevaluation of the dicyclic arene-homospermidine conjugates

Four novel dicyclic arene-homospermidine conjugates （6a-d） were synthesized and evaluated for cytotoxicity in L1210, α- difluoromethylomithine （DFMO） treated L1210, melanoma B16, spermidine （SPD） treated B16, and Hela cells. In the DFMOtreated L 1210 experiments, 6a-d were more sensitive to DFMO than naphthalene-homospermidine （6e）, suggesting that 6a-d can utilize the polyamine transporter （PAT） to enter the cells as well as 6e. The diminished cytotoxicity in the SPD/B 16 experiments also supported this conclusion. In summary, the homospermidine is an efficacious vector to ferry dicyclic arenes into cells via PAT.

Synthesis,DNA binding and topoisomerase inhibition of mononaphthalimide homospermidine derivatives

Two novel mononaphthalimide homospermidine derivatives （2a, 2b） with three or four methylene unit as linkages were synthesized and evaluated for cytotoxicity against human leukemia K562, murine melanoma B 16 and Chinese hamster ovary CHO cell lines. The presence of homospermidine motif could greatly elevate the potency of 1,8-naphthalimide. Conjugate 2b with longer spacer exhibited higher in vitro cytotoxicity than 2a. The DNA binding experiments indicated that conjugates 2b could bind to herring sperm DNA. The topoisomerase Ⅱ poison trials revealed that 2b could inhibit the activity of top. Ⅱ.

Synthesis and biological evaluation of hydrazino-containing polyamine skeletons as drug delivery system

A new series of polyamine-toxic cargo conjugates was synthesized with aryl aldehydes conjugating to hydrazino-containing triamine skeletons. The in vitro cytotoxicity of target compounds was evaluated in several cancer cell lines （e.g., L I 210, HeLa and B16） and the cellular entry of these polyamine conjugates via polyamine transporter was investigated on SPD- or DFMO-treated B 16 cell line. Of these compounds, 6c show significant cytotoxicity on L 1210, HeLa and B 16 cell lines （IC50 value, 3.74 μmol/L, 5.66μmol/L and 4.04 μmol/L, respectively）. The polyamine transporter assay demonstrated the suitability of hydrazino-containing polyamine backbones for application as vectors in drug delivery systems.