-
[show abstract]
[hide abstract]
ABSTRACT: Chemotherapy in treatment of malignant tumors has many side effects due to the poor physiochemical properties and the toxicity to normal tissues. The dual-targeting drug delivery system combining two high-affinity ligands can target anticancer drug primary to the diseased tissue, then to the tumor, which provides both greater efficacy of treatment and less harm to normal tissues. In this paper, a novel dual-targeting moiety RGD(7) (R-G-D-D-D-D-D-D-D; Nonapeptide for bone cancer combining D(6) peptide as bone target moiety and RGD peptide as tumors target moiety was contracted. A series of bone and/or tumor targeting conjugates have been synthesized in a convergent approach and well characterized by nuclear magnetic resonance (NMR) and mass spectrometry (MS) techniques. The hydroxyapatite (HAP) binding, water solubility, the drug release and the distribution in vivo were evaluated. All the conjugates were water-soluble and able to release the parent drugs in vitro. The bone-targeting property of the dual-targeting delivery system was enhanced from the results of the HAP binding and the distribution in vivo. The experiment for verifying tumor targeting property was underway. These results provided an effective entry to the development of a new dual-targeting delivery system for bone cancer.
Drug Delivery 09/2012; 19(7):317-26. · 1.46 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Bone tumor is a notoriously difficult disease to manage, requiring frequent and heavy doses of systemically administered chemotherapy. Targeting anticancer drug to the bone after systemic administration may provide both greater efficacy of treatment and less frequent administration. In this paper, a series of bone targeting Asp oligopeptides 5-fluorouracil conjugates have been synthesized in a convergent approach and well characterized by NMR and MS techniques. Their hydroxyapatite (HAP) affinity, drug release and cytotoxicity characteristics were evaluated in in vitro conditions. All the prodrugs were water soluble and exhibited high affinity to HAP .The efficient release of the active drug moiety occurring by the cleavage of different linkage in physiological conditions significantly reduced the number of viable human cancer cells. From in vivo distribution, we get these compounds with high bone-selectivity and long halflife. These results provided an effective entry to the development of new bone targeting chemotherapeutic drugs.
Bioorganic & medicinal chemistry 06/2011; 19(12):3750-6. · 2.82 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: To design and synthesize novel peroxisome proliferator-activated receptor gamma (PPARgamma) agonists.
A series of novel PPARgamma agonists were designed based on the binding character of PPARgamma agonists and the distribution of pharmacophore. The target compounds were synthesized using p-hydroxybenzaldehyde, 1, 2-dibromoethane, phenol, hydantoin and 2-thiohydantoin as materials.
Twelve compounds were synthesized by etherification and Knoevenagle condensation.
The target compounds were efficiently synthesized under mild condition and the structures of the target compounds were confirmed by 1HNMR and MS.
Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition 07/2010; 41(4):700-2.
-
[show abstract]
[hide abstract]
ABSTRACT: In this study, a series of aspartate based dendrimers with different cores were synthesized in a convergent approach and well characterized by NMR and MS techniques. The aqueous solubility of the model drugs (L-Histidine, Naproxen, Methotrexate) was measured in the presence of this kind of dendrimers at room temperature in PBS buffers at pH 6, 7 and 8. Results clearly confirmed that the solubility enhancement was due to presence of dendrimers at different pH compared to their corresponding aqueous solubility at different pH. The results indicated that the aspartate based dendrimers could be considered as an effective supplement of PAMAM dendrimers in solubility enhancement and drug delivery. The surface groups played an important role in dendrimer-mediated solubility enhancement.
European journal of medicinal chemistry 02/2010; 45(6):2705-11. · 3.27 Impact Factor
