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.

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.

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 and antitumor and antibacterial evaluation of fluoroquinolone derivatives(Ⅲ):Mono- and bis-Schiff-bases

To further explore an efficient modified route for the shift from an antibacterial fluoroquinolone to an antitumor one,mono-Schiff bases 6a-6h related to ciprofloxacin C3 carbonylhydrazone and bis-Schiff bases 4a-4h corresponding to C3/C7 carbonylhydrazone/hydrazone attached on a skeleton of ciprofloquinolone were designed and synthesized,and their in vitro antitumor activity against CHO,HL60,L1210 cells and antibacterial activity against Staphylococcus aureus and Escherichia coli were also reported.

Synthesis and antitumor evaluation of fluoroquinolone C3 fused heterocycles(Ⅱ):From triazolothiadiazines to pyrazolotriazoles

To further expand an effective modified route for the shift from an antibacterial fluoroquinolone （FQ） to an antitumor FQ, two series of title compounds based on an isostere of the FQ C3 carboxylic group with two fused heterocyclic rings, [ 1,2,4]triazolo[3,4- b][1,3,4]thiadiazine and pyrazolo[5,1-c][1,2,4]triazole, respectively, were designed and synthesized starting from the current antibacterial FQs, and their in vitro antitumor activity against L1210, CHO cell lines were evaluated via their respective IC50 values.