ABSTRACT
Analysis of methanol extraction residue (MER) from Bacillus Calmette-Guerin (BCG) was carried out to determine some specific chemical compositional characteristics. Samples of MER were found to contain approximately 40% protein and/or peptide, 3% soluble lipids, 17% bound lipids, 8% elemental nitrogen, and less than 2% mycolic acids. Amino acid analysis showed the presence of alanine, glycine and glutamic acid as the major amino acids. The data are reported in terms of the range found for each constituent over the samples analyzed. Somewhat consistent results were obtained between different MER preparations, but notable compositional variations were observed in samples of MER suspensions.
Subject(s)
Mycobacterium bovis/analysis , Amino Acids/analysis , Bacterial Proteins/analysis , Chemical Phenomena , Chemistry , Lipids/analysis , Methanol , Mycolic Acids/analysis , Nitrogen/analysisABSTRACT
By utilizing new types of producing microorganisms and isolating these on rather unusual growth media, we hope to produce new classes of antitumor drugs. In the detection system, we included the highly sensitive L1210 in vitro assay. But be requiring additional antimicrobial activity, we were able to eliminate rather early most of the previously known drugs from further work-up. The screening protocol was arranged so as to detect antimetabolites of a few rationally selected compounds.
Subject(s)
Antineoplastic Agents/pharmacology , Animals , Antibiotics, Antineoplastic/isolation & purification , Antibiotics, Antineoplastic/pharmacology , Antimetabolites, Antineoplastic/pharmacology , Asparagine/metabolism , Bacteria/drug effects , Bacteria/metabolism , Carbohydrate Metabolism , Cells, Cultured , Culture Media , Drug Evaluation, Preclinical/methods , Glutamine/metabolism , Leukemia L1210/metabolismABSTRACT
Chartreusin has exhibited significant therapeutic activity against three experimental mouse tumors (ascitic P388, L1210 leukemia, and B16 melanoma) when tumor cells were inoculated i.p. and drug was administered i.p. In further testing against P388 leukemia, no activity was observed when drug was administered p.o., s.c., or i.v. Chartreusin was very slowly absorbed from the small intestine, thus explaining the lack of activity when administered p.o. When given i.p., the drug precipitated in the peritoneal cavity and was slowly absorbed over several hr. The strong activity observed by this route was related to the prolonged and intimate contact of drug with tumor cells in the peritoneal cavity. Upon s.c. administration, extensive precipitation occurred. Subsequent dissolution and absorption from the injection site were very slow, and measured plasma and tissue levels were quite low. Biliary excretion of chartreusin, the predominant route of elimination. was very rapid, with 80 to 100% of the dose appearing as unchanged drug in the bile within 6 hr after i.v. administration. Rapid biliary excretion after i.v. administration was reflected in a rapid decline in plasma and tissue concentrations to levels (shown by in vitro cell kill experiments) less than those necessary to kill P388 cells. When the bile ducts of i.v.-dosed leukemic mice were ligated, therapeutic activity was observed, confirming that the physiological disposition of chartreusin exerts a major influence on its therapeutic utility.
Subject(s)
Antibiotics, Antineoplastic/therapeutic use , Leukemia, Experimental/drug therapy , Melanoma/drug therapy , Animals , Antibiotics, Antineoplastic/administration & dosage , Antibiotics, Antineoplastic/analysis , Antibiotics, Antineoplastic/metabolism , Benzopyrans , Bile/metabolism , Female , Glycosides/metabolism , Glycosides/therapeutic use , Injections, Intraperitoneal , Intestine, Small/metabolism , Leukemia L1210/drug therapy , Leukemia L1210/metabolism , Leukemia, Experimental/metabolism , Liver/metabolism , Male , Melanoma/metabolism , Mice , Mice, Inbred C57BL , Mice, Inbred DBA , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/metabolism , RatsABSTRACT
The NCI's antineoplastic fermentation program is reviewed. Clinically useful antitumor antibiotics are discussed in terms of their activity, mechanism of action, and the producing microbe.
Subject(s)
Antibiotics, Antineoplastic , Actinomycetales/metabolism , Antibiotics, Antineoplastic/isolation & purification , Bleomycin/isolation & purification , Bleomycin/therapeutic use , Chemical Phenomena , Chemistry , Dactinomycin/isolation & purification , Dactinomycin/therapeutic use , Daunorubicin/isolation & purification , Daunorubicin/therapeutic use , Drug Evaluation, Preclinical , Fermentation , Humans , National Institutes of Health (U.S.) , Neoplasms/drug therapy , Plicamycin/isolation & purification , Plicamycin/therapeutic use , Sterigmatocystin/analogs & derivatives , Sterigmatocystin/isolation & purification , Sterigmatocystin/therapeutic use , Streptomyces , United StatesABSTRACT
The production of trans-cinnamic acid from various alkylbenzenes by soil microorganisms was studied intensively by use of a co-oxidation technique. The microorganisms were grown on n-paraffins, and they did not use aromatic compounds as a carbon source when the preferred substrate was present in the medium. The effects of cell population, co-oxidation time, and type and mode of addition of the alkylbenzenes on the yield of trans-cinnamic acid were investigated. Yields (5 g/liter) of a product consisting of trans-cinnamic acid (88 to 100%) and 5-phenylvaleric acid (0 to 12%) were obtained when the proper conditions were chosen. Of a variety of microorganisms studied, a soil isolate closely related to Cellulomonas galba was found to be best for the production of trans-cinnamic acid.
