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Biomedical subjects

F E Hahn

Publications and source records attributed to F E Hahn.

At least 37 records · Page 2Linked to original sources
PubMed1975

Strategy and tactics of chemotherapeutic drug development.

Strategic approaches to generating chemotherapeutically active lead compounds are either empirical as in traditional synthetic programs or in the search for antibiotics; they are semiempirical as concerns the design of antimetabolites and more rational for the design of DNA-complexing drugs. The tactics of exploitation of active lead compounds in chemotherapeutic drug development involve molecular modification. This aims at either substances with greater activity and/or substances with improved pharmacokinetic parameters. From quantitative structure-activity relationships one might extrapolate to members of a chemical series with improved pharmacokinetic properties. Scientific advances render chemotherapy research more predictive and, hence, less empirical.

Animals↗
PubMed1975

Bacteriological studies with morphine-like narcotics: relevance to narcotic actions in mammals?

A search for active bacterial growth inhibitors among seven highly potent morphine-like narcotics revealed that NIH 7591 and etorphine inhibited the rates of growth of Escherichia coli by 50% at 1.9 x 10(-4) M. Bacterial cultures escaped from growth inhibition by NIH 7591 after times which were proportional to the drug concentrations and inversely proportional to the initial bacterial densities. Populations of E. coli could adapt to resist and cross-resist growth inhibitions by NIH 7591 and phenazocine. Resistance was lost after growth in drug-free medium for a few doubling times. The agonist-antagonist pair, etorphine and diprenorphine, inhibited growth of E. coli additively without any indication of antagonism. Actions of narcotics in bacteria is considered a theme in its own right.

Drug Synergism↗
PubMed1975

Incorporation of double-labeled L-cystine and DL-valine in penicillin.

l-[3,3'-(3)H]cystine was incorporated into penicillin with retention of one tritium. This result can be explained by beta-lactam formation through ring closure between C3 of cysteine and NH of valine. No radioactivity of dl-[2,3-(3)H]valine was incorporated into penicillin. The loss of isotope at C2 occurs during the inversion of configuration. The loss of label at C3 is discussed in terms of possible intermediates for the formation of the thiazolidine ring of penicillin.

Carbon Radioisotopes↗
PubMed1974

R factors in strains of Salmonella typhi and Shigella dysenteriae 1 isolated during epidemics in Mexico: classification by compatibility.

All 17 Salmonella typhi strains tested from the epidemic in Mexico carried R factors of compatibility group H, conferring resistance to chloramphenicol, streptomycin, tetracycline, and sulfonamides. Some S. typhi strains carried, in addition, non-conjugative, ampicillin resistance plasmids and R factors of the I or A-C complex. All 20 Shigella dysenteriae 1 strains tested of epidemic origin carried O-group R factors. Ampicillin resistance in S. dysenteriae 1 was not proved to be plasmid borne. R factors of group H were not identified in any of the tested Mexican isolates other than S. typhi, but R factors of group O were identified in Escherichia coli, Shigella flexneri, and one strain of S. typhi, as well as in the epidemic S. dysenteriae. An R factor was identified which seemed to have two compatibility specificities, groups Iomega and O.

Disease Outbreaks↗
PubMed1972

Mode of action of primaquine: preferential inhibition of protein biosynthesis in Bacillus megaterium.

The growth of a strain of Bacillus megaterium was prevented by a minimal inhibitory concentration of primaquine of 52 mug/ml or 2 x 10(-4)m. When exponentially growing cultures received the drug at 6 x 10(-4)m, the rate of growth was drastically reduced and no further growth occurred after 15 min of exposure. At this concentration, primaquine was bactericidal, causing a 50% reduction in the viable population after one doubling time of 45 min. Supplying primaquine to cultures 30 min after adding radioactive-labeled phenylalanine, thymidine, uracil, or diaminopimelic acid produced an immediate and complete inhibition of protein biosynthesis but no inhibition of deoxyribonucleic acid biosynthesis for at least 15 min, and caused the formation of ribonucleic acid and cell wall polymer to proceed linearly at rates similar to those established prior to the addition of drug. This pattern of inhibition of macromolecular biosyntheses suggests that the major in vivo action of primaquine in B. megaterium is to block protein synthesis.

Amino Acids↗
PubMed1971

Bactericidal action of 2-hydroxy-3-(cyclohexylpropyl)-1,4-naphthoquinone on Bacillus megaterium.

The antimalarial drug, 2-hydroxy-3-(cyclohexylpropyl)-1,4-naphthoquinone (NQ), at concentrations of approximately 10(-5)m (3 mug/ml), was bactericidal for the gram-positive bacterium, Bacillus megaterium. Only a few other gram-positive bacteria were sensitive to this drug. All growth inhibitory concentrations of NQ were also bactericidal for B. megaterium, and even resting suspensions of cells were killed. The incorporation of radioactive-labeled leucine, thymidine, uracil, and diaminopimelic acid into protein, deoxyribonucleic acid, ribonucleic acid, and the cell wall polymer was arrested immediately and completely upon addition of NQ to cultures in exponential growth. NQ produced a delayed effect on aerobic respiration and no change in the rate of oxygen consumption was observed at a time when all major biosyntheses had failed. (3)H-NQ was demonstrated to bind strongly and preferentially to the bacterial cell membrane. This simultaneous shutdown of all major categories of in vivo macromolecular syntheses points to an effect of NQ upon membrane-centered energy supplying reactions or transport of essential nutrients, or both.

Anti-Bacterial Agents↗
PubMed1971

Antibacterial nitroacridine, Nitroakridin 3582: effects on bacterial growth and macromolecular biosynthesis in vivo.

The antibacterial drug Nitroakridin 3582 inhibited the growth of selected grampositive bacteria more strongly than it inhibited the growth of gram-negative bacilli. Nitroakridin at concentrations of the order of 5 x 10(-5)m induced lysis of Bacillus licheniformis and Micrococcus lysodeikticus. At concentrations less than 10(-4)m, Nitroakridin 3582 reduced the exponential growth rate of Escherichia coli C-2; at 10(-4)m the drug was bacteriostatic, and, at concentrations greater than 10(-4)m, it was bactericidal. Prolonged bacteriostasis resulted in the formation of long filaments by E. coli, Serratia marcescens, Shigella sonnei, and Proteus mirabilis. The reversible effects of Nitroakridin 3582 on the growth of E. coli correlated with partial inhibitions of deoxyribonucleic acid biosynthesis; ribonucleic acid and protein syntheses were inhibited less strongly. Nitroakridin 3582 at concentrations greater than 2 x 10(-4)m, which block deoxyribonucleic acid biosynthesis, produced an accelerated bactericidal action.

Acridines↗
PubMed1971

Antibacterial nitroacridine, Nitroakridin 3582: binding to nucleic acids in vitro and effects on selected cell-free model systems of macromolecular biosynthesis.

Nitroakridin 3582 (NA) formed complexes with native deoxyribonucleic acid (DNA) and with transfer ribonucleic acid (tRNA) species from Escherichia coli. Spectrophotometric titrations of NA with these nucleic acids produced numerical results from which nonlinear adsorption isotherms were derived. These curves indicated the existence of more than one class of binding sites on the polymers to which NA was bound by more than one process. The stoichiometry of strong binding of NA to double helical DNA was in agreement with a conventional value (1 ligand molecule per 4.2 component nucleotides) for complete intercalation binding. NA inhibited the DNA-dependent DNA polymerase I and RNA polymerase reactions, the first strongly and the second appreciably. These inhibitions corresponded to the extents to which NA inhibits DNA and RNA biosyntheses in vivo. Evidently, NA interferes with the template function of DNA. The drug also inhibited the polymerization of phenylalanine in a cell-free E. coli ribosome-polyuridylic acid [poly (U)] system. The effect paralleled an inhibition of the poly (U)-directed binding of phenylalanyl tRNA to ribosomes. Ethidium bromide acted similarly. The antimalarial drug, chloroquine, stimulated polyphenylalanine synthesis, apparently as a result of stimulating the poly (U)-directed binding of phenylalanyl tRNA to ribosomes.

Acridines↗
PubMed1971

Streptomycin.

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Amino Acid Sequence↗