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Biomedical subjects

K H Büchel

Publications and source records attributed to K H Büchel.

At least 19 recordsLinked to original sources
PubMed1988

Sterol biosynthesis inhibitors. Secondary effects and enhanced in vivo efficacy.

Sterol biosynthesis inhibitors such as the imidazoles and 1,2,4-triazoles are generally regarded as inhibitors of sterol C-14 demethylation. Neither the MIC values nor the data for direct interaction with the cytochrome P-450 responsible for oxidative C-14 methyl removal, however, fully explain the observed in vivo efficacy. The first generation of azoles, which includes clotrimazole and miconazole, has been supplemented by a second generation, and azoles of the new generation are capable of additional effects on sterol biosynthesis. With the new azoles, for example, delta 5 sterols may accumulate, the accumulation being due to additional sites of inhibition in sterol biosynthesis or to direct membrane-azole interactions. Ketoconazole, itraconazole, and vibunazole are representative of the azoles of the second generation. Finally, a third generation of azoles has been discovered. Azoles of this generation, which include fluconazole, show almost negligible in vitro potency against saprophytically grown fungi but excellent in vivo efficacy. These compounds specifically affect parasitic forms of fungi, thus blocking invasion processes, and interfere directly with the plasma membrane, as shown in leakage experiments. Such secondary effects obviously enhance in vivo potency.

Antifungal Agents↗
PubMed1983

Antimycotic efficacy of bifonazole in vitro and in vivo.

The new imadozolyl derivative 1-(p, alpha-diphenyl-benzyl)imidazole (bifonazole, Bay h 4502, Mycospor) shows in vitro the broad spectrum of activity characteristic of azole antimycotics. The intensity of activity under conventional test conditions is equivalent to that of clotrimazole. Further, concentrations of less than or equal to 5 micrograms/ml bifonazole have a fungicidal effect on dermatophytes, and a MIC value of less than or equal to 0.25 micrograms/ml has a maximal effect on Torulopsis glabrata. In ng concentrations bifonazole is effective on proliferating dermatophytes and pseudomycelia of Candida albicans. The resistance situation regarding bifonazole is favourable--as is typical of azole antimycotics. In animal experiments, topical application of concentrations of between 0.05 and 1% bifonazole as a cream or solution are extremely effective on guinea-pig trichophytosis. This is attributed to the therapeutically achievable fungicidal effect on dermatophytes and the long period of time the substance is retained in the skin. The sum of the experimental properties of bifonazole make it possible to recommend the active drug to be applied, once every 24 h, as a 1% cream or solution and the duration of therapy for these indications being reduced to 2-3 weeks.

Animals↗
PubMed1979

[Concepts for the synthesis of new biologically active substances].

Three concepts for the synthesis of biologically active compounds are discussed and illustrated by examples. In addition to the accidental finding of biologically active compounds, synthesized purely for chemical reasons, analogy models can serve as guidelines for synthesis. In the latter, naturally occurring or synthetic biologically active molecules are modified to optimize or alter the biological properties. A third approach for the synthesis of active substances is oriented according to the side of action. Models from biochemistry and molecular biology serve as a basis for synthesis planning.

Biochemical Phenomena↗