Tumor coils which have both saccharidase and tyrosinase activity are selectively treated by administration of a conjugate of a cytotoxic compound which is a substrate for tyrosinase and at least one saccharide or a pharmaceutically acceptable salt or ester thereof. Among the cytotoxic phenolic compounds which are substrates for tyrosinase which can be used are 4-hydroxyanisole, butylated hydroxyanisole, L-3,4-dihydrophenylalanine, dopamine, tertbutylcatechol, hydroquinone, resorcinol, 6-hydroxydopa, and methyl gallate. The efficacy of the treatment is enhanced by also administering a compound that inhibits the action of glutathione reductase.

Co Enzyme Technology Ltd.

Method and compositions for treating tumors having high tyrosinase activity

Tumor cells which have .beta.-glucuronidase and tyrosinase activity are selectively treated by administration of a conjugate of a cytotoxic compound which is a substrate for tyrosinase and glucuronic acid or a pharmaceutically acceptable salt or ester thereof particularly the methyl-triacetylated form of glucuronic acid. Among the cytotoxic phenolic compounds which are substrates for tyrosinase which can be used are 4-hydroxyanisole, butylated hydroxyanisole, L-3,4-dihydroxy-phenylalanine, dopamine (3,4-dihydroxyphenethylamine), terbutylcatechol, hydroquinone, resorcinol, 6-hydroxydopa (3,4,6-trihydeoxyphenylalanine) and methyl gallate.The efficacy of the treatment is enhanced by also administering a compound that inhibits the action of glutathione reductase.

The mechanism of action of Ebselen differentiates between bacterial and mammalian thioredoxin reductase (TrxR). It displays fast oxidation of mammalian Trx and via the NADPH-TrxR catalyzed turnover of ebselen selenol with hydrogen peroxide, and therefore are mammalian antioxidants. Ebselen, and its diselenide, are strong competitive inhibitors of E. coli TrxR with K.sub.i of 0.14 .mu.M and 0.46 .mu.M, respectively. E. coli mutants lacking glutathione reductase or glutathione were much more sensitive to inhibition by ebselen. Since either glutaredoxin or thioredoxin systems are electron donors to ribonucleotide reductase, ebselen targets primarily glutathione and glutaredoxin-negative bacteria, a class which includes major pathogens. Ebselen, and similar compounds are therefore useful as antibacterial agents, even for multiresistant strains. Two major pathogenic bacteria, which previously had not been known to be sensitive to ebselen, Mycobacterium tuberculosis (tuberculosis) and Helicobacter pylori (stomach ulcer and cancer), were shown to be excellent targets. Helicobacter pylori was also sensitive to ebsulfur.

Holmgren; Arne

Lu; Jun

Vlamis-Gardikas; Alexios

Zhao; Rong

Kandasamy; Karuppasamy

Engman; Lars

Engstrand; Lars

Hoffner; Sven

Thioredoxin Systems AB

Bacterial thioredoxin reductase inhibitors and methods for use thereof

The present invention related to safe plant drug for treatment of liver disease, specifically, this invention proves a safe plant drug Schisandrin and its preparation. Schisandrin has the following pharmaceutical functions: increasing tumor suppresson genes express activity, decreasing activity of oncogenes, increasing immune function, increasing liver DNA synthesis, decreasing serum alamine aminotransferase activity, increasing glutathione level, increasing glutathione reductase activity, decreasing lipid peroxidation of liver, increasing hepatic microsomal monooxygenases activity, increasing ATP content in liver, increasing energy metabolism activity, decreasing density lipoprotein oxidation, protecting gastrointestinal function, increasing killer cell activity, increasing complement activity, decreasing induced liver cancer activity and decreasing grown of cancer cells.

Plant drug for treatment of liver disease