Growth-inhibiting concentrations

A 50% growth inhibition concentration in vivo. Ratio of life-span of the treted mice to that of the control mice. 

Analog number Compound stablM"1] (EtOH, 25 °C) Antimicrobial activity against Staphylococcus aureus UV-3 (minimal growth inhibiting concentration pg/ml)... 

When reacted with dimethyl acetylenedicarboxylate, the amines produced ben-zotriazolylaminobutendioates 188 accompanied by A-benzotriazolyl substituted 2-pyridones only in the case of 5-amino-2-methyl-2//-benzotriazole, the triazolo-9,10-dihydrobenzo[d]azepine and an unusual cyclization product, triazolo-2-oxindole (convertible into 2-methyltriazolo[4,5-/]carbostyril-9-carboxylate) were formed. The quinolones 189 were aromatized to chloroesters 190 these in turn were hydrolyzed to chloroacids 191 and decarboxylated to 9-chlorotriazolo[4, 5-/]quinolines 192 (Scheme 58) (93H259). The chlorine atom could be replaced with 17 various secondary amines to give the corresponding 9-aminoalkyl(aryl) derivatives 193, some of which exhibit both cell selectivity and tumor growth inhibition activity at concentrations between 10 and 10 " M (95FA47). 

In the commonest form of microbiological assay used today, samples to be assayed are applied in some form of reservoir (porcelain cup, paper dise or well) to a thin layer of agar seeded with indicator organism. The drug diffuses into the medium and after incubation a zone of growth inhibition forms, in this case as a circle around the reservoir. All other factors being constant, the diameter of the zone of inhibition is, within limits, related to the concentration of antibiotic in the reservoir. 

TABLE 7.3 Concentrations in pg/mL that Cause 50% Growth Inhibition (GI5o) ... 

Table 7.3 shows the concentrations of 1-5 that result in 50% growth inhibition (GI50) of five human cancer cell lines. Inspection of these data reveals that cytostatic activity of 1 and 3-5 depends on the thermodynamic favorability of the quinone methide species compared to the corresponding keto form. The most cytostatic prekinamycins 1 and 5 are associated with the thermodynamically stable quinone methides. In contrast, the inactive prekinamycins 3 and 4 are associated with thermodynamically stable keto tautomers. The exception is prekinamycin 2, which is cytostatic and possesses a relatively stable keto tautomer 3 compared to its quinone methide. Although the AE value for quinone methide tautomerization can predict cytostatic properties, prekinamycin 2 shows that there must be other factors determining biological activity. 

Figure 1. Linear regression plot of tomato and radish seedling root growth inhibition with varying concentrations of phenyl aliphatic acids. Benzoic acid (V) phenylacetic acid (X) 3-phenyIpiropanoic acid (A) 4-phenylbutanoic acid ( ) trans-cinnamic acid (----) (1).

Figure 4. Regression analysis of radish root growth inhibition with concentration (ppm). (T) g-Hydroxybenzaldehyde, y=56.34g " x (-) prunasin, =56. (A) g-hydroxymandelonitrile,...

The antiproliferative properties of clavulone I (88) were studied in greater detail using the HL60 leukemia cell line [128]. Application of the natural product at 0.4 pM (0.2 pg ml 1) irreversibly decreased the growth rate of these cells to half that of controls. Complete growth inhibition was observed at about 1.0 pM and cytotoxicity was observed at higher concentrations. 

It was therefore concluded that ethylene is the gas X postulated by Johnson and Gamow. The concentration necessary to cause 50% inhibition of the bending rate is 30 ppm, which although low is not as low as the concentration of ethylene which effects higher plants [0.1 ppm in pea growth inhibition, Abeles (1973)]. 

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