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Biomedical subjects

F E Hahn

Publications and source records attributed to F E Hahn.

At least 19 recordsLinked to original sources
PubMed1977

Changes in superhelical density of closed circular deoxyribonucleic acid by intercalation of anti-R-plasmid drugs and primaquine.

The following compounds, which possess anti-R-plasmid activity (Hahn and Ciak, 1976) in decreasing order, were shown by viscometric titration to change systematically the superhelical density of closed circular PM2 deoxyribonucleic acid in the manner of intercalators: ethidium bromide, quinacrine, acridine orange, quinine, chlorpromazine, chloroquine, and methylene blue. The same effect was caused by the antimalarial drug primaquine, which has not been tested for antiplasmid activity.

Acridines↗
PubMed1976

Elimination of resistance determinants from R-factor R1 by intercalative compounds.

Eighteen deoxyribonucleic acid (DNA)-complexing compounds, among them 15 intercalative substances, and, additionally, nalidixic acid eliminated with different frequencies four antibiotic resistance determinants from the R-factor R1, carried by Salmonella typhimurium. Eliminating concentrations did not inhibit growth of the bacteria. The most active compound was "nitroacridine II" {1-diethylamino-3-[(6-nitro-9-acridinyl)amino]propanol}. When 14 compounds which had been tested at a standard concentration of 10(-4) M were listed according to decreasing activities of elimination of the four resistance determinants, a nearly consistent activity sequence was revealed. Frequencies of elimination of the kanamycin resistance determinant correlated directly with the binding of compounds to DNA, i.e., with end points of their displacement of methyl green from the methyl green-DNA complex. We propose that the observed eliminations resulted from selective toxicity for plasmidic template DNA and inhibitions of R-factor replication.

Culture Media↗
PubMed1975

Studies on the Methyl Green-DNA complex and its dissociation by drugs.

Spectrophotometric results indicated that Methyl Green bound stably to native calf thymus DNA and to poly[d(A-T)] but to a lesser extent to phiX 174 DNA, tRNAs, and poly(dG-dC), a copolymer that exists preferentially in the A conformation. Exposing the Methyl Green-DNA complex to graded concentrations of ethyl alcohol liberated part of the dye slowly by a zero-order reaction; higher alcohol concentrations which cause the B leads to A transition of DNA released the bulk of Methyl Green. The viscosity of the Methyl Green-DNA complex was significantly lower than that of the uncomplexed DNA. The dye was progressively liberated from DNA by 1.5 x 10(-1) M NaCl and by much lower concentrations of Mg2+; in its stoichiometric complex with DNA, it increased Tm by approximately 12 degrees C. A series of DNA-complexing drugs displaced Methyl Green from DNA at exponential rates and to end points which were correlated. End points of displacement correlated with the abilities of drugs to unwind supercoiled DNA, to labilize ribosomes to heat, and to eliminate a kanamycin resistance determinant from an R factor carried by Salmonella typhimurium. Additional correlations between Methyl Green displacement and biochemical-biological activities of displacing drugs are cited. In conjunction with these findings, our results suggest that Methyl Green displacement analysis is a useful biochemical screen for the detection or development of biologically active compounds which bind to DNA.

Animals↗
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↗