Synthesis and biological evaluation of novel steroid-linked nitrogen mustards

Two novel steroid-linked nitrogen mustard conjugates la and lb were synthesized by using estrogenic acid 4 coupled with aniline mustard 8 and phenol mustard 13 in an esterification or amidation procedure. Preliminary cytotoxic screening on cancer cell lines in vitro showed that, the steroid-ester linked nitrogen mustard conjugate la exhibited obvious increasing of activities.

Synthesis of porphyrin nitrogen mustards with potential anti-tumor activities in chemotheraphy and photodynamic therapy

2,7,12,18-Tetramethyl-13,17-di[3'-N,N'-di(2'-chloroethyl)aminopropyl]porphin and it's 3,8-di(1'-alkyloxyethyl)-analogous or porphyrin-nitrogen mustards were synthesized for the first time Their structures were determined by spectroscopics and elemental analyses.Most of the compounds possess both the chemotherapeutic and photodynamic effects on tumor and deserve further investigation.

Design and Synthesis of Glycosylated Aromatic Nitrogen Mustard Derivatives

Antibody-directed enzyme prodrug therapy（ADEPT） is a new strategy for the treatment of cancer that has arisen in recent twenty years, the main merits of which are that it can improve the selectivity of anticancer drugs and reduce the side effects in remote tissue. In the present study, two prodrugs-glycosylated aromatic nitrogen mustard derivatives were synthesized. Glucose and lactose were converted into glycosyl donors-trichloroacetimidate; the obtained glycosyl donors were glycosylated with p-nitrophenol （ glycosyl donors） to form β-glucosyl p-nitrobenzene and β-lactosyl p-nitrobenzene that were protected by acetyl in a stereoselective manner; the two products were reduced by zinc dust and then treated with ethylene oxide, afforded two glycosylated nitrogen mustard derivatives that were protected by acetyl; the last step was to deacetylate and then afforded the two target compounds that could be used as prodrugs of ADEPT for further Anti-tumor research.

Lethal Effect of Benzene Nitrogen Mustard Glucoside Derivate on K562 Cells

A new synthesized benzene nitrogen mustard was converted into glycosyl donor-trichloroacetimidate that was glycosylated with p-nitrophenol（glycosyl donors） to form β-lactosyl p-nitrobenzene under the protection of acetyl in a stereoselective manner, was prepared and evaluated for its cytotoxicity towards cultured K562 cell line. Methylthiazoy tetrazolium（MTT） assay, transmission electron microscopy（TEM）, flow cytometry（FCM） and immunohistochemistry were utilized to explore the mechanisms of how the compound arrests the growth of HCT-T cells. This new synthesed benzene nitrogen mustard glucoside derivate（BNMGD） presented a lower toxicity to normal cells, but is significantly more toxic to K562 cells compared with nitrogen mustard, meanwhile it can induce the apoptosis of K562 cells. These results indicate that the new synthesized BNMGD can inhibit the growth of K562 cells and induce the apoptosis, and its cytotoxicity towards cultured K562 cell line is much more effective than that of nitrogen mustard.

Palliative Local Radiotherapy in the Treatment of Tumor-stage Cutaneous T-cell Lymphoma/ Mycosis Fungoides

Objective To determine the efficacy of palliative radiotherapy in treating tumor-stage cutaneous T-cell lymphoma/mycosis fungoides(MF).Methods From January 2008 to January 2013,a total of 11 patients with tumor-stage MF were treated with local radiation therapy in Peking Union Medical College Hospital.The median age of these patients was 53.36±14.45 years.Female-male ratio was 1:1.2.The average course of disease was 10.82±3.37 years.All the patients were treated with local electronic beam irradiation with a total median dosage of 48.55±9.51(40-74) Gy in an average of 24.55±5.57(20-40) fractions,5 fractions per week.Results The median follow-up time was 55.27±29.3(13-103) months.No severe acute or chronic side effects of irradiation were observed.Complete clinical response(CR) rate of the radiated sites was 54.5%(6/11),partial response(PR) rate was 36.4%(4/11),and the overall response rate(CR+PR) was 90.9%.One patient showed no response.Conclusion Local radiotherapy with psolaren plus ultraviolet A and/or interferon maintaining treatment is an effective palliative therapy in the treatment of tumor-stage MF patients.

Synthesis and Characterization of Thiophene-derived Amido Bis-nitrogen Mustard and Its Antimicrobial and Anticancer Activities

The thiophene-derived amido bis-nitrogen mustard N2,N2,N5,N5-tetrakis（2-chloroethyl）-3,4-dimethylthio- phene-2,5-dicarboxamide was designed and synthesized via five-step reactions from commercially available 2-chloroacetonitrile. This target compound was confirmed by 1H NMR, 13C NMR, MS, IR spectra and elemental analyses, and its structure was further characterized by X-ray single-crystal analysis. The biological activities for the title compound and some intermediates were evaluated in vitro for their antibacterial, antifungal and cytotoxic activities. The preliminary results showed that the title compound could inhibit efficiently the growth of the tested microorganisms including drug-resistant bacteria MRSA to some extent. Moreover, the target compound was found to be effective against prostatic carcinoma cell line （PC-3）, breast carcinoma cell line （MCF-7）, colon carcinoma （LoVo） and lung cancer （A549）. Especially, it gave selective antitumor efficacy against prostatic carcinoma cell line （PC-3） at a low dose. Keywords nitrogen mustard, thiophene, antibacterial, antifungal, cytotoxicity

Separation of chiral phosphorus compounds on the substituted P-cyclodextrin stationary phase in normal-phase liquid chromatog-raphy

The separation of enantiomers of a series of eighteen novel nitrogen mustard linked phosphoryl diamide derivatives was investigated on the prepared phenyl carbamate derivative β-cy-clodextrin bonded phase in normal-phase HPLC. Some of the enantiomers could be separated in baseline. The chiral recognition mechanism was also suggested for the separation of chiral phosphorus organic compounds.