65202-29-1

Herein hybrid silica nanoparticles have been engineered to direct the sequential delivery of multiple chemotherapeutic drugs in response to external stimuli such as variations in pH. The nanocarriers consist of conventional MCM-41-type nanoparticles, which have been functionalised with an organic ligand (or stalk) grafted onto the external surface. The stalk is designed to recognise a complementary molecule, which serves as a cap to block the pores of the nanoparticles. First, camptothecin is introduced into the pores by diffusion prior to capping the pore apertures via molecular recognition. The cap, which is a derivative of 5-fluorouracil, serves as a second cytotoxic drug for synergistic chemotherapy. In vitro tests revealed that negligible release of the drugs occurred at pH 7.4, thus avoiding toxic side effects in the blood stream. In contrast, the stalk/cap complex is destabilised within the endolysosomal compartment (pH 5.5) of cancer cells, where release of the drugs was demonstrated. Furthermore, this environmentally responsive system exhibited a synergistic effect of the two drugs, where the pH-triggered release of the cytotoxic cap followed by diffusion-controlled release of the drug cargo within the pores led to essentially complete elimination of breast cancer cells.

Disclosed are conjugates including a recognition element covalently bonded to or linked through a linker to a payload. The payload is a pharmaceutical agent (e.g., an antineoplastic agent, anti-infective agent, or anti-inflammatory agent) or a diagnostic agent. Also disclosed are methods of using the conjugates.

γ-Aminopropylsilatrane has been reported to possess biological activity against tumor cancer cells with low cytotoxicity in many kinds of silatranes. So some N-substituted γ-aminopropylsilatrane derivatives were synthesized and assayed by a primary antica

The disclosure includes hydroxamic compounds of Formula I: (I) wherein P, Z, and m are defined herein. Also disclosed is a method for treating a neoplastic disease or an immune disease with these compounds.

This application discloses embodiments of a novel prodrug and its method of synthesis. The prodrug comprises a galactose-containing polysaccharide covalently linked to 5-fluorouracil (5-FU). The galactose residues that are part of the backbone of the gala

This invention describes a novel polysaccharide prodrug of 5-fluorouracil (5-FU) with enhanced target specificity for colorectal cancer treatment, and its preparation methods. The prodrug is synthesized by chemically linking anti-cancer drug 5-fluorouraci

New 1-carbamoyl-5-fluorouracil conjugates which consist of a combination of 5-fluorouracil and anti-ulcer derivatives were designed in order to investigate their antitumor activity toward gastric carcinoma.The synthesis of these new analogs was achived using a coupling reaction between 1-chloroformyl-5-fluorouracil and 1-(ω-aminoalkyl) derivatives of well-known anti-ulcer compounds, ie, omeprazole and cimetidine. - Keywords: 5-fluorouracil; 1-carbamoyl-5-fluorouracil; omeprazole; cimetidine.

Fifty-four 1-carbamoyl-5-fluorouracils were synthesized from 5- fluorouracil and isocyanate or amine. Antitumor activity was tested in the L- 1210 tumor system and 11 compounds gave better values of therapeutic ratio than HCFU (1-hexylcarbamoyl-5-fluorouracil). 1-(4- Methoxycyclohexylcarbamoyl)-5-fluorouracil gave the best result.

1-(Nitroxylureido)-5-fluorouracils were obtained by the reaction of isocyanatonitroxyl radicals with 5-fluorouracil or aminonitroxyl radicals with 5-fluoro-1-(chloroformyl)-uracil.

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