Bioautographs

We have long been Interested in the possibility that the cardiovascular effects of carboxylic lonophores could be harnessed to provide new drugs for the treatment of disease states such as heart failure and shock. There may, however, be subpopulations of man for whom lonophores may be particularly toxic. For example, a toxic Interaction between monensln and digitalis on the dog heart has been reported (37). Our oral absorption data do Indicate that If a useful human therapeutic application can be established, lonophores could be administered as drugs orally. 

ACS Symposium Series American Chemical Society Washington, DC, 1980. 

It appears urgent that we Increase our understanding In depth of the physiological and metabolic effects of lonophores and their pharmacological and toxicological ramifications. 

Ovchinnikov, Yu.A, Ivanov, V.T. Shkrob, A.M. Membrane-Active Complexones Elsevier New York, 1975 Vol. 12. 

Westley, J.W. Klrk-Othmer Encyclopedia of Chemistry and Technology WlleyrNew York, 1978 pp. 47-64. 

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Physical methods, some of which can be applied in the on-line mode (Fig. 8) and physiological methods providing information concerning the effectivity of the separated substance can be used. A later volume will treat these bioautographic methods which can be subdivided into bioassays (off-line) and bioautogrammes (on-line). 

Saponins la 7,411,430 -, bioautographic determination la 109 Sarcosine Ia435 lbl24 Scandium cations, detection la 144 Scanner, optical trains la 30,39 S-Chamber (small chamber) la 126,127 SCHiFF s bases lb 52 Scintillators la 12 Scopolamine lb 231,252,255,323 Scopoletin lb 216-218,365 Screening process lb 45 Sebacic acid la 178,233,249,308 Sebuthylazine lb 418 Selectivity, enhancement by derivatiza-tion la 55... 

Some of the early reports on the chromatography of the tetracycline antibiotics prior to 1957 are of limited value. Fischbach and Levine (43) described a continuous ascending technique and Berti and Cima (44) reported an ascending method using aqueous sodium arsenite as the mobile solvent. Other authors(45,46) reported descending techniques and bioautographic means for locating the zones of activity. 

The description of alternative bioautographical systems will be found in section 6.34.)... 

Peterson, C.A. and Edgington, E.V. Ouantitative estimation of the fungicide benomyl using a bioautograph technique, J. Agric. Food Chem., 17(4) 898-899, 1969. 

In 2001, Greger et al. isolated the stress-induced carbazole phytoalexins carbalexin A (57), B (58), and C (59) from the leaves of Glycosmis parviflora. These carbazole alkaloids showed strong antifungal activity in bioautographic tests on TLC plates with Cladosporium herbarum (86). 

LM Lewin, R Golan, O Wassercug, S Green. Bioautographic identification of coenzyme A, pantothenic acid and derivatives. J Micronutr Anal 4 209-216,1988. 

A sensitive and specific bioautographic method for the identification of choline and its derivatives, was developed by Lewin and Marcus, utilizing a Neurospora crassa mutant [5]. As little as 0.03 y of choline chloride is detectable. The applicability of the method for detection of choline derivatives in lipid hydrolyzate is discussed. A method for determining the rate of diffusion of compounds from paper chromatograms into bioautograph agar is described. 

Linnell, J.C. Hoffbrand, A.V. Peters, T.J. Matthews, D.M. Chromatographic and bioautographic estimation of plasma cobalamins in various disturbances of vitamin B12 metabolism. Clin. Sci. 1971, 40, 1-16. 

No antibacterially active metabolites of amoxicillin were detected in human urine by TLC with bioautographic detection using Bacillus subtilis on agar gel [145],... 

Many penicillins, including penicillin V, are metabolized in the human body to other active compounds. Rolinson and Batchelor 140 administered the drugs orally or by intramuscular injection and evaluated both blood and urine samples by paper chromatography. Active metabolites were detected by bioautographic plates. Vanderhaeghe, Parmentier and Evrard 141 identified the major metabolite of penicillin V as p-hydroxyphenoxy-methyl penicillin. It represented about 10% of the microbiological activity in the urine. A small amount of o-hydroxyphenoxymethyl penicillin was also observed while in the urine of some patients another metabolite was detected. They speculated this might be the dihydroxy derivative. 

Methods useful to detect cephalosporins on chromatograms are short wave (254 nm) ultraviolet light, ninhydrin spray, sodium hydroxide-iodine-starch spray l, and bioautographs using Bacillus subtilis ATCC 6633 ... 

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