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Biomedical subjects

C K Chu

Publications and source records attributed to C K Chu.

At least 127 records · Page 7Linked to original sources
PubMed1977

Effects of long-term exposure to environmental levels of polychlorinated biphenyls on pharmacokinetics of pentobarbital in rats.

The pharmacokinetics of pentobarbital, 30mg/kg iv, were studied in untreated rats and rats pretreated with 1,5, and 25 ppm of polychlorinated biphenyls in food for up to 140 days. Environmental contaminants may contribute to variations in metabolic rates of drugs by causing enzyme induction. The objective of this work was to quantitate the effects of environmental levels of the contaminant and enzyme inducer, a polychlorinated biphenyl, on the pharmacokinetics of pentobarbital, a drug whose primary elimination route is liver metabolism. The pharmacokinetics of pentobarbital in rats could be fit to a biexponential equation of the type Cp = Ae-alpha t+ Be-beta t. After 35 days of pretreatment, only the 25-ppm-treated rats showed any significant acceleration of pentobarbital elimination. At the 70- and 140-day samplings, both the 5- and 25-ppm pretreatments showed significant acceleration of pentobarbital elimination. There were no significant effects on A, alpha, B, and Vd for any pretreatment. The beta-values for the 25-ppm-pretreated rats reached a constant value from the 35-day pretreatment period onward. A calculation of total body clearance suggested that pentobarbital elimination in those rats had approached portal blood flow rate-limited metabolism.

Animals↗
PubMed1977

Synthesis and inhibition analysis of 2(4)-imino-4(2)-amino-2,4-dideoxyriboflavin, a dual antagonist of riboflavin and folinic acid.

The synthesis of the 2,4-diamino analogue of riboflavin is described. Inhibition analysis in a microbial assay system indicated that this compound has a weak antifolate activity that could be overcome with a minimal amount of folinic acid, but at higher concentrations both folinic acid and riboflavin were required for the reversal of its inhibitory effect.

Depression, Chemical↗
PubMed1977

Nucleosides. CVI. Syntheses of 1-N-methyl-5-(beta-D-ribofuranosyl)uracil (1-N-methyl-phi-uridine) and its identity with a metabolite elaborated by Streptomyces platensis var. clarensis.

Very recently, 1-N-methyl-psi-uridine was isolated from the culture filtrate of Streptomyces platensis var. clarensis along with an antibacterial and antiviral antibiotic, U-44590. We achieved chemical syntheses of 1-N-methyl-psi-uridine by selective methylation of psi-uridine in two different routes and established the identity of the synthetic nucleoside with the natural product.

Chemical Phenomena↗
PubMed1976

Antileukemic effects of pseudoisocytidine, a new synthetic pyrimidine C-nucleoside.

Pseudoisocytidine, a new synthetic pyrimidine C-nucleoside, which might be considered a more stable analog of 5-azacytidine, is active in vitro and in vivo, i.p. and p.o., against various 1-beta-D-arabinofuranosylcytosine-resistant lines of mouse leukemia. This antileukemic activity is blocked by cytidine but not by deoxycytidine or thymidine.

Animals↗
PubMedDate not supplied

Asymmetric synthesis of oxazolidine nucleosides and related chemistry.

Asymmetric synthesis of N-substituted oxazolidinyl nucleosides has been accomplished from L-isoserine, trans- and cis-Oxazolidine intermediates (4 and 5) were stereoselectively constructed from N-protected L-isoserine with a menthoxycarbonyl group by the condensation with benzoyloxy acetaldehyde dimethyl acetal in a ratio of 3.9 to 1 in favor of trans-isomer 4. The major isomer 4 was converted to enantiomerically pure beta- and alpha-N-L-menthoxycarbonyl oxazolidinyl thymine nucleosides 11 and 12 in 6 steps.

Antiviral Agents↗
PubMedDate not supplied

L-nucleoside analogues as potential antimalarials that selectively target Plasmodium falciparum adenosine deaminase.

The L-stereoisomer analogues of D-coformycin selectively inhibited P. falciparum adenosine deaminase (ADA) in the picomolar range (L-isocoformycin, Ki 7 pM; L-coformycin, Ki 250 pM). While the L-nucleoside analogues, L-adenosine, 2,6-diamino-9-(L-ribofuranosyl)purine and 4-amino-1-(L-ribofuranosyl)pyrazolo[3,4-d]-pyrimidine were selectively deaminated by P. falciparum ADA, L-thioinosine and L-thioguanosine were not. This is the first example of 'non-physiological' L-nucleosides that serve as either substrates or inhibitors of malarial ADA and are not utilised by mammalian ADA.

Adenosine Deaminase Inhibitors↗
PubMedDate not supplied

Synthesis of L-3'-hydroxymethylribonucleosides.

The target compounds were synthesized via the key intermediate carbohydrate 8, which was synthesized by first selectively protecting the 1'- and 2'-hydroxyl groups followed by selective tosylation of the 5'-hydroxyl group to obtain compound 3. The tosyl moiety was then replaced by a benzyl either to obtain 4. Compound 4 underwent Dess-Martin oxidation to afford the ketone 5. Compound 5 was subjected to Wittig olefination to afford the alkene 6 followed by regioselective hydroboration to obtain 7. Compound 7 was fully acetylated using acetic acid, acetic anhydride and sulfuric acid to obtain the key intermediate 8.

Acetylation↗
PubMedDate not supplied

Synthesis and antiviral activities of enantiomeric 1-[2-(hydroxymethyl) cyclopropyl] methyl nucleosides.

Cyclopropyl carbocyclic nucleosides have been synthesized from the key intermediate 2 which was converted to the mesylated cyclopropyl methyl alcohol 3. Condensation of compound 3 with various purine and pyrimidine bases gave the desired nucleosides. All synthesized nucleosides were evaluated for antiviral activity and cellular toxicity. Among them adenine 22 and guanine 23 derivatives showed moderate antiviral activity against HIV-1 and HBV. None of the other compounds showed any significant antiviral activities against HIV-1, HBV, HSV-1 and HSV-2 in vitro up to 100 microM.

Anti-HIV Agents↗
PubMedDate not supplied

New classes of fluorinated L-nucleosides; synthesis and antiviral activity.

The synthesis of 3'-fluorinated apionucleosides 7 and 2'-fluoro-2',3'-unsaturated L-nucleosides 8 via common synthon, 2-fluoro-butenolide 2, has been described. Among the newly synthesized nucleosides, L-2'-F-d4C, L-2'-F-d4FC and L-2'-F-d4A exhibit significant anti-HIV and anti-HBV activities.

Antiviral Agents↗
PubMedDate not supplied

L-purine nucleosides as selective antimalarials.

L-nucleosides selectively enter malaria infected erythrocytes and have the unique ability to be metabolised by the malarial adenosine deaminase. This has allowed us to design novel L-nucleosides as potential anti-malarials.

Adenosine Deaminase↗