1.Strengthen the works of management of the pro-drug and chemical for illegal production of stupefacients
Pharmaceutical Journal 1998;262(2):4-5
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
2.Lead compound optimization strategy (3)--Structure modification strategies for improving water solubility.
Zeng LI ; Jiang WANG ; Yu ZHOU ; Hong LIU
Acta Pharmaceutica Sinica 2014;49(9):1238-1247
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
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Prodrugs
;
chemistry
;
Solubility
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Structure-Activity Relationship
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Water
;
chemistry
3.A Case of Doxifluridine-Induced Multiple Atypical Moles on the Palm and Sole of a Patient Taking Immunosuppressive Agents.
Woon Kyong CHUNG ; Seong Min KANG ; Do Young RHEE ; Sung Eun CHANG ; Mi Woo LEE ; Jee Ho CHOI ; Kee Chan MOON
Korean Journal of Dermatology 2008;46(9):1257-1261
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
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Female
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Floxuridine
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Fluorouracil
;
Humans
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Hyperpigmentation
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Immunosuppressive Agents
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Prodrugs
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Pyrimidines
4.Liposomes as Acitivators of Lipophilic Platinum (2 ) Complexes.
Journal of the Korean Cancer Association 1999;31(1):180-187
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
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Hydrogen-Ion Concentration
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Liposomes*
;
Platinum*
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Prodrugs
5.Preparation of curcumin prodrugs and their in vitro anti-tumor activities.
Peng, LU ; Qiangsong, TONG ; Fengchao, JIANG ; Liduan, ZHENG ; Fangmin, CHEN ; Fuqing, ZENG ; Jihua, DONG ; Yuefeng, DU
Journal of Huazhong University of Science and Technology (Medical Sciences) 2005;25(6):668-70, 678
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
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Curcumin/*pharmacology
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Dose-Response Relationship, Drug
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Prodrugs/*chemical synthesis
;
Prodrugs/*pharmacology
;
Tumor Cells, Cultured
;
Urinary Bladder Neoplasms/*pathology
6.A review of the expression and activity of drug metabolism enzymes in tumorous cells.
Wen-jing XIAO ; Guang-ji WANG ; Ji-ye A
Acta Pharmaceutica Sinica 2014;49(10):1377-1386
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
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pharmacokinetics
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Cell Line, Tumor
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Humans
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Inactivation, Metabolic
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Liver
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metabolism
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Neoplasms
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enzymology
;
Prodrugs
;
pharmacokinetics
7.5-Aminolevulinic acid esters based photodynamic therapy.
Sujuan ZHANG ; Zhenxi ZHANG ; Dazong JIANG
Journal of Biomedical Engineering 2002;19(2):310-314
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
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pharmacology
;
Esters
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pharmacology
;
Photochemotherapy
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Photosensitizing Agents
;
pharmacology
;
Prodrugs
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Protoporphyrins
;
pharmacology
8.Identification of a new azoreductase driven prodrug from bardoxolone methyl and 5-aminosalicylate for the treatment of colitis in mice.
Xin QIAO ; Yan GONG ; Yi MOU ; Yi-Hua ZHANG ; Zhang-Jian HUANG ; Xiao-Dong WEN
Chinese Journal of Natural Medicines (English Ed.) 2021;19(7):545-550
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
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Colitis/drug therapy*
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Mesalamine/pharmacology*
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Mice
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Nitroreductases
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Oleanolic Acid/pharmacology*
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Prodrugs
9.Research of oral prodrugs: opportunities and challenges.
Feng CAO ; Qi-Neng PING ; Jun CHEN
Acta Pharmaceutica Sinica 2008;43(4):343-349
Prodrug is an effective way to improve the oral absorption of the drugs which belong to Biopharmaceuticals Classification System (BCS) class III and IV. This review addresses the progress of the oral prodrugs in recent years, mainly including classical prodrug design and targeted prodrug design. Classical prodrug design is focused on modification of oil-water partition coefficient or decrease the metabolism of parent drugs. Targeted prodrug design is actively concerned with the physiological characteristics of the gastrointestinal tract to target tissues, enzymes and influx transporters. Intestinal influx transporter, the peptide transporter-targeted prodrug design is a growing field of the research of oral prodrugs recently. Challenges of prodrug strategy, design and investigation in vivo are also discussed.
Administration, Oral
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Animals
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Biological Transport
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Drug Delivery Systems
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Drug Design
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Humans
;
Intestinal Absorption
;
Prodrugs
;
administration & dosage
;
pharmacokinetics
;
Solubility
10.Biocatalytic desymmetric hydrolysis of 3-(4-chlorophenyl)-glutaronitrile to the key precursor of optically pure baclofen.
Meizhen XU ; Jie REN ; Jingsong GONG ; Wenyue DONG ; Qiaqing WU ; Zhenghong XU ; Dunming ZHU
Chinese Journal of Biotechnology 2013;29(1):31-40
We produced (S)-4-cyano-3-(4-chlorophenyl)-butyrate by highly stereoselective biocatalyst in this study. A nitrilase-producing strain, named Gibberella intermedia WX12, was isolated by 3-(4-chlorophenyl)-glutaronitrile as substrate in the screening with phenol-sodium hypochlorite method. The fermentation conditions and catalytic properties of this strain were investigated. The preferred carbon and nitrogen sources for nitrilase production were lactose (30 g/L) and peptone (20 g/L). After being cultivated for 96 h, the cells were collected for use in biotransformation. The hydrolysis of 3-(4-chlorophenyl)-glutaronitrile was performed at 30 degrees C in phosphate buffer (pH 8.0, 50 mmol/L) for 24 h to give (S)-4-cyano-3-(4-chlorophenyl)-butyric acid with 90% yield and > 99% of ee, which can be used for the synthesis of (R)- and (S)-baclofen. The configuration of product was determined by chemically converting it to baclofen and comparison with the authentic sample by chiral HPLC analysis.
Aminohydrolases
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metabolism
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Baclofen
;
chemical synthesis
;
chemistry
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Biocatalysis
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Chlorophenols
;
chemistry
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Gibberella
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enzymology
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Hydrolysis
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Nitriles
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chemistry
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Prodrugs
;
chemical synthesis
;
chemistry