Bacterial antitumor activity

A link between bacteria and tumor therapy was found early, at the beginning of the XVIII century [10]. By the end of the XIX century, Coley [11] developed a treatment for cancer with a mixture of bacterial toxins. In 1943 Shear and Turner [4] found that the antitumor effect of Coley s toxin was due to endotoxins, and after several decades it was shown that the biological activity of LPS was due to the lipid A [5]. We investigated the structures of lipids A with regard to their antitumor activities [12], finding that the optimum in vivo activity is obtained with diglucosamines acylated by 3 long chain fatty acids. 

Cyclic enyne allenes are also reactive. Neocarzinostatin is a bacterial antibiotic that also shows antitumor activity. Here, the occurrence of a Myers-Saito Cyclization sets the stage for the cleavage of DNA ... 

A host of bismuth compounds has been used for studies involving antibacterial and antitumor activities and warfare agents. It should be noted that many of the compounds are no longer in use, because with the advent of other natural compounds these metallic species are used very little. The most common compounds used to date are bismuth subcitrate or bismuth subsalicylate as bacterial intestinal agents and for action against ulcers (Pepto-bismol Proctor and Gamble). In both cases these were provided as colloidal agents which had limited water solubility. 

Adams and coworkers21 also examined the chemical composition and antitumor activity of polysaccharide fractions obtained from the Temple University strain of S. marcescens grown in a medium containing sucrose. Some fractions were obtained from bacterial cells by repeated extraction with aqueous phenol, followed by digestion with... 

The toxicity of polycarboxylic acid polymers is more sensitive to polymer structure and molecular weight than antitumor activity. The acute toxicity is markedly decreased with decreasing molecular weight (Table VI and XI). Further,polyanion polymers have been shown to highly sensitize mice to bacterial endotoxin (39)> this activity is strikingly molecular weight dependent as shown in Tables VII and XI as well as dose dependent ( 3. The enhanced sensitivity to endotoxin by synthetic anionic polymers has been extensively studied, but the mechanism of action is still not understood (39)-... 

Another enzyme for which X-ray diffraction studies have aided in an analysis of the mode of action is the enzyme dihydrofolate reductase. This catalyzes the reduction of 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate, an essential coenzyme used in the synthesis of thymidylate, inosinate, and methionine. The antitumor agent methotrexate is a powerful inhibitor of dihydrofolate reductase, causing, on binding, a cellular deficiency of thymidylate (the cause of its antitumor activity). The crystal structures of the enzyme from two bacterial sources—Escherichia coli and Lactobacillus casei—and from chicken liver have been studied (88-90). Both the E. coli and L casei enzymes have been studied as complexes with methotrexate bound at the active site, and, in the case of the . casei enzyme, the cofactor, NADPH, was also present. 

Cisplatin was discovered during electrolysis experiments of bacterial culture media utilizing platinum electrodes. An electrode product exhibited antibacterial activity at very low concentrations. The product, cisplatin, also revealed antitumor activity. Cisplatin crosslinks DNA via ring atoms of purines and possibly pyrimidines, with the elimination of Cl analogously to the bifunctional alkylating agents discussed. Although c/s-platinum can be... 

An ansamycin antibiotic produced by Streptomyces spectabilis with antibacterial (against tuberculosis pathogens), antiviral, and antitumor activities. S. occurs as a multi-component mixture of up to ten individual compounds (S. A to G, J, K, and U) with S. C (methyl streptovaricate, C4oH5,NO,4, Mr 769.84, amorphous, mp. 189-191 °C, [a][) 4-602°) as the main component. The S. are inhibitors of bacterial RNA-polyme-rase as well as the reverse transcriptase of oncogenic viruses. The biosynthesis of the aromatic core branches off from the shikimic acid pathway while the alkyl chain is formed on the polyketide pathway. 

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