Bioassays, antibacterial

A structural feature common to all previously-described and widely-used compounds is that the acylamino substituents on C-6(7) next to the lactam carbonyl are in the j8-configuration. Bioassays reveal that the epipenicillins (94) and epicephalosporins (95) having an acylamino side-chain in the a-configuration exhibit negligible antibacterial properties [180,181]. The first example of such compounds was epihetacillin, obtained from hetacillin by treatment with triethylamine [182]. The lack of activity can be explained in accordance with the mode of action of /3-lactam antibiotics [183] in the case of the epi-derivatives the structural similarity between the terminal D-alanyl-D-alanine moiety and the antibiotic molecule no longer exists. Details will be discussed in the section on the mode of action. 

F. foliacea also occurs in the Bay of Fundy, Canada. Bioassay-guided fractionation based on antibacterial activity of the extract of this bryozoan has lead to the isolation of a different series of bromoal-kaloids of the physostigmine class, two of which were N-oxides (39]. The major alkaloids were dihydroflustramine C, 90, ( 60%), which had been reported previously by these authors [40) and flustramine D, 91, (-40%). Minor alkaloids found were dihydroflustramine C N-oxide, 92. flustramine D Af-oxide, 93, and isoflutramine D, 94. The JV-oxides were also synthesised by oxidation of the corresponding free bases with m-chloroperbenzoic acid. These alkaloids were shown to be responsible for the wide spectrum of antibacterial activity exhibited by this bryozoan extract. 

A1 Dabbas et al. [163] reported the antibacterial activity of the ethyl acetate extract of the whole aerial part of Varthemia iphinoides L. The bioassay-guided fractionation led to the isolation and identification of an antibacterial eudesmane sesquiterpene, selina-4,ll(13)-dien-3-on-12 oic acid. Fig. (10). This compound exhibited potent antimicrobial activity against 6 bacterial species Staphylococcus aureus, Bacillus subtilis. Micrococcus luteus, Escherichia coli. Bacillus cereus and Salmonella enter Hides ). The MIC values of this sesquiterpene, which was determined by the agar dilution method, ranged between 250 and 500 ig/ml. 

Flavonoids are natural polyphenolic substances widely distributed in the different parts of plants such as fruits, bark, stems, roots, leaves and flowers. Structurally they are characterized by a pyran ring or a similar structure of three carbons. These polyphenolic compounds are well known for displaying a remarkable spectrum of biological activities, including antibacterial and antifungal properties. In the Anthemideae tribe, some of these compounds were isolated by bioassay-guided fractionation, after previously detecting antimicrobial activity on the part of the plant. 

Bioassay-guided fractionation of an extract of Artemisia annua was conducted in order to assess the possible presence in the plant material of inhibitors of bacterial multidrug resistance pumps [218]. Fractions were tested for Staphylococcus aureus growth inhibition in the presence of a subinhibitory dose of weak antibacterial alkaloid berberine. Active fractions yielded the flavones chrysoplenol D and chrysoplenetin,... 

The bioassay-guided fractionation of the ethanolic and etheric leaf and inflorescence extracts from Centaurea ruprestis yielded the flavonoid quercetagetin T-methyl ether 7-O-p-D-glucopyranoside [27]. The antimicrobial spectrum of quercetagetin was broad, but weak for Gram (-) bacteria and moderate for dermatophytes. Specifically, it showed antibacterial activity against Klebsiella pneumoniae, Escherichia coli. Salmonella java and Serratia spp. 

In this chapter, a rationale of the structure-activity relationships of various series of bioactive secondary metabolites from Indo-Pacific marine invertebrates is reviewed. These include alkaloids, terpenes and polybrominated diphenyl ethers which were subjected to a series of bioassays in search for insecticidal, antibacterial, fungicidal, and cytotoxic lead compounds. From these various biotests, it was observed that the bioactivity of an analogue is not due to general toxicity but rather possesses a degree of specificity on a particular target biomolecule. The relationship between chemical structures and biological activity is related to the specific action of a compound. 

For the cytotoxicity against mouse lymphoma cells, renierone and 1,6-dimethyl-7-methoxy-5,8-dihydroisoquinolin-5,8-dione were found to be the most active derivatives with EC50S of 1.1 p,g/mL and 1.7 ig/mL, respectively. From the results obtained, in the described bioassays, it is obvious that the antibacterial and fungicidal activity of the compounds under study is not paralleled by the insecticidal activity towards neonate... 

Both in vitro and in vivo activity is reduced by an increase in the acyl group length in the 2 -0-acyl derivatives. The MIC values of the 2 -0-acetyl and 2 -0-propionyl derivatives are nearly the same as that of the parent antibiotic. Because the 2 -0-acyl is easily hydrolyzed in aqueous solution, the potent antibacterial activity has been explained by the hydrolysis of 2 -0-acyl group during bioassays. For this reason, the 2 -hydroxyl group has been considered to be one of the functional groups essential for the biological activity of the macrolide. 

Tasteless crystals from dil methanol, dec 171-173. Mg + 115.3 (c = 10 in chloroform). Potency 939 units/mg. Soly in water 9 units/ml (bioassay). Solubilities determined by Weiss et al. Antibiot. A Chemother. 7, 374 (1957) iu mg/ml at about 28 Water 0.075 methanol 7.3 ethanol 5.2 isopropanol 1.7 isoamyl alcohol 3.1 cyclohexane 0.115 benzene 0.60 toluene 0.39 peer etber 0.0 isooctane 0.055 carbon tetrachloride 0.50 ethyl acetate 1.65 isoamyl acetate 1.4 acetone 3.4 methyl ethyl ketone 3.65 ether 0.70. therap cat Antibacterial. 

Batista et al. (58) used an overlay method in the bioassay-guided fractionation of an acetone extract of the roots of Plectranthus hereroensis (Labiatae) to isolate the antibacterial diterpene (Compound 14). Staphylococcus aureus was used as the test organism. 

Nemorosone (58), and chamone I (69), isolated from floral resins and trunk latex of Clusia grandiflora respectively, showed pronounced antibacterial activity on honeybee pathogens Paenibacillus larvae and Paenibacillus alvei in TLC bioassay [9]. These compounds are structurally similar, differing only the degree of prenylation. Chamone II and methyl ethers of nemorosone and chamone I were inactive and this suggest that the presence of an enol functionality is necessary for antibacterial activity in these molecules. 

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