It is difficult to find the production facilities of the stupefacients because most of them are located in the remote areas. All pro-drug and chemicals for production are under the national and international control. Therefore, the illegal production of stupefacients can not be carried out without pro-drug and chemical. The name of crime for sales of pro-drugs regulated in the Article No 185 of the Criminal Law of Social republic of Vietnam.
Prodrugs ; Chemistry

Doxifluridine is a pyrimidine derivative and is activated to 5-fluorouracil by pyrimidine phosphorylase. Multiple acral hyperpigmented macules have been reported in patients treated with systemic 5-fluorouracil or some of its prodrugs. However, there have been no reports of this adverse event being induced by doxifluridine. Herein we present a 42-year-old woman with multiple pigmented lesions on the palm and sole after chemotherapy with oral doxifluridine.
Adult ; Female ; Floxuridine ; Fluorouracil ; Humans ; Hyperpigmentation ; Immunosuppressive Agents ; Prodrugs ; Pyrimidines

PURPOSE: The goal of this study is to understand the activation processes that take place within the liposomal formulation of lipophilic diaminocyclohexane platinum (DACH-Pt) complexes, to identify the activated species of this class of compounds, and to use that information to develop a reproducible liposomal formulation of DACH-Pt complexes. MATERIALS AND METHODS: Liposomal DACH-Pt complexes were prepared by lyophilization-rehydration method using PC, PG and PA. Their intraliposomal stability and biological activity were determined by HPLC and in vitro/in vivo experiments. RESULTS: DACH-Pt complexes in a liposomal formulation have shown significant promise in preclinical studies and clinical phase I, II trials. Interestingly, they are prodrugs which converts into one or more undetennined activated platinum species within the liposomes ex vivo. Our studies have shown that the stability of liposomal DACH-Pt complexes is inversely related with the antitumor activity of those complexes. The configuratian of leaving group in the complexes and pH of the liposome suspension affect significantly the degradation/activation process that takes place within the liposomes. DACH-Pt complexes with linear (L10) leaving groups are more stable than complexes with branched ones (B10 and NDDP), but also significantly less potent. The presence of PG and PA in the liposome is a prerequisite for the degradation/activation process of DACH-Pt complexes. As PG and PA formulation gave more dramatic changes of the original complexes than PC alone due to lower pH, the cytotoxicity and antitumor activity at those fonnulations increased against PC alone. DACH-Pt complexes are very stable in liposomes containing PC alone but inactive in vitro/in vivo experiments. CONCLUSION: These results also support that the active species produced within the liposomal DACH-Pt complexes is DACH-Pt-Cl2.
Chromatography, High Pressure Liquid ; Hydrogen-Ion Concentration ; Liposomes* ; Platinum* ; Prodrugs

Water solubility is an essential physical chemistry property of organic small molecule drug and is also a very important issue in drug discovery. Good water solubility often leads to a good drug potency and pleasant pharmacokinetic profiles. To improve water solubility, structure modification is a straight and effective way based on the theory of water solubility. This review summarized valid structure modification strategies for improving water solubility including salt formation, polar group introduction, liposolubility reduction, conformation optimization and prodrug.
Drug Design ; Prodrugs ; chemistry ; Solubility ; Structure-Activity Relationship ; Water ; chemistry

The curcumin prodrugs, which could be selectively activated in tumor cells, were prepared to establish a basis for the targeted chemotherapy for cancer. On the basis of the molecular structure of curcumin, the N-maleoyl-L-valine-curcumin (NVC), N-maleoyl- glycine-curcumin (NGC) were chemically synthesized and identified by IR and NMR spectroscopy. After treatment with these two prodrugs for 6 - 24 h, the rates of growth inhibition on human bladder cancer EJ cells and renal tubular epithelial (HKC) cells were detected by MTT colorimetry. Our results showed that after the treatment with 20 micromol/L - 40 micromol/L NVC and NGC for 6 - 24 h, the growth inhibitory effects on EJ cells were 6.71% - 65.13% (P < 0.05), 10.96% - 73.01% (P < 0.05), respectively, in both dose- and time-dependent manners. When compared with the curcumin of same concentrations, the growth inhibitory effects of these two prodrugs on HKC cells were significantly decreased (P < 0.01). It is concluded that activation of curcumin prodrugs via hydrolysis functions of cellular esterase could inhibit the growth activities of tumor cells, and reduce the side effects on normal diploid cells. This provided a novel strategy for further exploration of tumor-targeted chemotherapeutic drugs.
Antineoplastic Agents, Phytogenic/*pharmacology ; Curcumin/*pharmacology ; Dose-Response Relationship, Drug ; Prodrugs/*chemical synthesis ; Prodrugs/*pharmacology ; Tumor Cells, Cultured ; Urinary Bladder Neoplasms/*pathology

As exogenous ALA (5-aminolevulinic acid) esters can induce the production and accumulation of endogenous photosensitizer PpIX (protoporphyrin IX) in tumor tissues more effectively, they have been the most active photosensitizer prodrug in PDT(photodynamic therapy) field. In this article, along with the procedure of ALA esters based PDT, some primary mechanism and experimental results were considered, which include: first, cellular uptake of ALA esters and its conversion into ALA; second, the production and accumulation of endogenous photosensitizer PpIX induced by eNdogenous ALA esters; last, the photosensitization of PpIX.
Aminolevulinic Acid ; pharmacology ; Esters ; pharmacology ; Photochemotherapy ; Photosensitizing Agents ; pharmacology ; Prodrugs ; Protoporphyrins ; pharmacology

Tumorous cells are characterized by distinctive metabolic reprogramming and living conditions. Understanding drug metabolizing features in tumor cells will not only favor the estimation of metabolic rate, elimination half life and the assessment of potency, but also facilitate the optimal design of anti-tumor drugs/prodrugs. This article reviewed the expression and activity features of major drug metabolizing enzymes (DMEs) in solid tumorous tissues, such as liver, intestine, breast and lung, and the difference from the correspondingly normal tissues, exemplified by the metabolic properties of some classic antitumor-agents in tumorous tissues. In combination with the data retrieved in vitro tumor cell lines, we discussed the similarities and differences of DMEs expression and function between tumor tissues (in vivo) and tumor cells (in vitro), and proposed the possible factors that cause the differences.
Antineoplastic Agents ; pharmacokinetics ; Cell Line, Tumor ; Humans ; Inactivation, Metabolic ; Liver ; metabolism ; Neoplasms ; enzymology ; Prodrugs ; pharmacokinetics

For local treatment of ulcerative colitis, a new azoreductase driven prodrug CDDO-AZO from bardoxolone methyl (CDDO-Me) and 5-aminosalicylate (5-ASA) was designed, synthesized and biologically evaluated. It is proposed that orally administrated CDDO-AZO is stable before reaching the colon, while it can also be triggered by the presence of azoreductase in the colon to fragment into CDDO-Me and 5-ASA, generating potent anti-colitis effects. Superior to olsalazine (OLS, a clinically used drug for ulcerative colitis) and CDDO-Me plus 5-ASA, CDDO-AZO significantly attenuated inflammatory colitis symptoms in DSS-induced chronic colitis mice, which suggested that CDDO-AZO may be a promising anti-ulcerative colitis agent.
Animals ; Colitis/drug therapy* ; Mesalamine/pharmacology* ; Mice ; Nitroreductases ; Oleanolic Acid/pharmacology* ; Prodrugs

Gastric cancer remains a significant problem in terms of global health, and is the most common cancer in Korea. Surgery is the only potentially curative treatment for localized gastric cancer, but most cases present at an advanced stage. Randomized trials have demonstrated that chemotherapy for advanced gastric cancer improves the quality of life and extends survival, by 4~6 months, compared with best supportive care alone. Single agents with a proven activity in a first-line setting include 5-fluorouracil (5-FU), doxorubicin, mitomycin C, cisplatin, taxanes (docetaxel and paclitaxel) and oral fluoropyrimidines (capecitabine and TS-1). Based on the results from several large scale randomized trials, FP (5-FU/cisplatin) and ECF (epirubicin/cisplatin/5-FU) combinations are the most widely used regimen against advanced gastric cancer. Phase II studies of the FP and ECF combination reported a 40~51% response rate in previously untreated patients, and this regimen also produced a significantly higherresponse rate than the FAM (5-FU/doxorubicin/ mitomycin) and FAMTX (5-FU/doxorubicin/methotrexate) regimens, respectively. However, significant treatment related- toxicities and discomfort were reported from ECF, which prevents this combination from becoming the standard treatment regimen. While no one combination chemotherapy regimen is accepted as the standard for advanced gastric cancer, FP is currently considered a suitable reference regimen worldwide. New agents, such as taxane, irinotecan and oxaliplatin, combined with old agents, such as cisplatin and 5-FU, are currently under evaluation to further improve treatment outcomes. Also, oral 5-FU prodrugs are replacing the cumbersome 5-FU long-term infusion due to its convenience and superior toxicity profile. However, the low complete response rate and short response duration are still the main obstacles in the chemotherapy for gastric cancer. Only large scale comparative clinical trials will give clues to improve the results of gastric cancer treatments.
Cisplatin ; Doxorubicin ; Drug Therapy* ; Drug Therapy, Combination ; Fluorouracil ; Humans ; Korea ; Mitomycin ; Palliative Care ; Prodrugs ; Quality of Life ; Stomach Neoplasms* ; Taxoids

PURPOSE: Uridine-cytidine kinase (UCK) 2 is a rate-limiting enzyme involved in the salvage pathway of pyrimidine-nucleotide biosynthesis. Recent studies have shown that UCK2 is overexpressed in many types of cancer and may play a crucial role in activating antitumor prodrugs in human cancer cells. In the current study, we evaluated the potential prognostic value of UCK2 in breast cancer. METHODS: We searched public databases to explore associations between UCK2 gene expression and clinical parameters in patients with breast cancer. Gene set enrichment analysis (GSEA) was performed to identify biological pathways associated with UCK2 gene expression levels. Survival analyses were performed using 10 independent large-scale breast cancer microarray datasets. RESULTS: We found that UCK2 mRNA expression was elevated in breast cancer tissue compared with adjacent nontumorous tissue or breast tissue from healthy controls. High UCK2 levels were correlated with estrogen receptor negativity (p<0.001), advanced tumor grade (p<0.001), and poor tumor differentiation (p<0.001). GSEA revealed that UCK2-high breast cancers were enriched for gene sets associated with metastasis, progenitor-like phenotypes, and poor prognosis. Multivariable Cox proportional hazards regression analyses of microarray datasets verified that high UCK2 gene expression was associated with poor overall survival in a dose-response manner. The prognostic power of UCK2 was superior to that of TNM staging and comparable to that of multiple gene signatures. CONCLUSION: These findings suggest that UCK2 may be a promising prognostic biomarker for patients with breast cancer.
Biomarkers ; Breast Neoplasms* ; Breast* ; Dataset ; Estrogens ; Gene Expression ; Humans ; Neoplasm Metastasis ; Neoplasm Staging ; Phenotype ; Prodrugs ; Prognosis* ; RNA, Messenger ; Uridine Kinase*