Structure-activity relationships of protoberberines having antimicrobial activity

13-Alkyl derivatives (2-6 and 8-12) of berberine (1) and palmatine (7) were subjected to in vitro antibacterial activity tests against Bacillus subtilis and Salmonella enteritidis. Antibacterial activity increased as the length of the C-13 aliphatic side chain increased. The effects of the oxygen-substituents on aromatic rings A, C, and D of protoberberinium salts 13-20 on the antimicrobial activity against Staphylococcus aureus, B. subtilis, S. enteritidis, Escherichia coli, and Candida albicans are also discussed. The change in lipophilicity of the protoberberinium salts caused by modification of the substituents appears to influence the antibacterial activity. 13-Hexylberberine (6) and 13-hexylpalmatine (12) exhibited the greatest antibacterial activity.     

In vitro selection for different mutational patterns in the HIV-1 reverse transcriptase using high and low selective pressure of the nonnucleoside reverse transcriptase inhibitor HBY 097

Measurement of Na-Ca exchange activity was used to examine subsarcolemmal sodium levels ([Na+]s) in single, voltage-clamped guinea-pig cardiac myocytes while Na-K pump activity was modulated pharmacologically. Changes in Nas were evaluated from phase-plane analysis of the changes in intracellular calcium, measured using the fluorescent indicators Fura-red and Fluo-3. Activation of beta-adrenoceptors with 1 microM isoprenaline resulted in activation of the cAMP-dependent chloride current, but had no effect on the calcium transient mediated via the Na-Ca exchanger, regardless of whether the Na-K pump was active or inhibited (with strophanthidin). The ability of Na-Ca exchange activity to report [Na+]s was demonstrated by the effect of changing the extracellular rubidium concentration from 1 to 5.4 mM to modulate Na-K pump activity. We suggest that beta-adrenergic stimulation does not directly affect either the Na-K pump or the Na-Ca exchanger and that the Na-Ca exchanger can be used as a sensitive indicator of changes in [Na+]s and Na-K pump activity.     

Structure-activity relationships of phomactin derivatives as platelet activating factor antagonists

Phomactins, natural products isolated from the culture broth of marine fungus Phoma sp., were found to be active as PAF antagonists. This unique carbon skeleton led us to investigate the structure-activity relationship demonstrating that the lipophilicity at C-(7-8), acetoxy, (methoxycarbonyl)oxy, and 3-isoxazolyloxy substitution at C-20, and 2-beta-OH configuration at C-2 are all required for the enhancement of inhibitor activity.