Secondary mode of action

Deris ZZ, Akter J, Sivanesan S, Roberts KD, Thompson PE, Nation RL, et al. A secondary mode of action of polymyxins against gram-negative bacteria involves the inhibition of NADH-quinone oxido-reductase OLCtivity.f Antihiot 2013 67 147-51. 

Mode of action research has caused similar challenges for investigators working with either natural products or synthetic pesticides. The major difficulty is to separate secondary effects from primary causes. Although effects can be measured in... 

The observation that allelcpathic agents affect plant growth and development leads the physiologist to question the modes of action. While we know that diverse secondary plant products exhibit allelopathic activity, it is difficult to understand the mechanism of action of these plant products partly because of ... 

Almost without exception the numerous transformations which primary and secondary nitroparaffins undergo involve the aci-iorm, i.e. they take place under conditions in which the salt of the oci-form is produced. Qualitatively the nitroparaffins greatly resemble ketones in their mode of action, although the much greater reaction velocity of the nitro-compounds brings about a quantitative difference. 

Secondary pharmacodynamic studies investigate the mode of action or effects of a substance not related to its desired therapeutic target. 

Genotoxic modes of action involve genetic alterations caused by the substance interacting directly with DNA to result in a change in the primary sequence of DNA. A substance can also cause genetic alterations indirectly following interaction with other cellular processes (e.g., secondary to the induction of oxidative stress). 

In the search for bioactive marine secondary metabolites, drugs or drug leads with new modes of action, many invertebrates with new modes of action have been explored and tested in a variety of assays. Many marine natural products were found to be cytotoxic to an assortment of tumor cells, Some parts of the marine natural products were also found to be ichthyotoxic so as to defend themselves. Two examples, out of many, are the latrunculins and sarcophine. ... 

Intoxicating chemicals are those that are not necessarily lethal (see Pesticides) but operate as primary repellents or secondary repellents, eg, emetics causing sickness or distress. Primary bird repellents are those whose mode of action is having a bad taste immediate rejection of food is the desired result. However, they are effective only if other foods are available they are not effective in times of food shortages, because large flocks of migrating birds would be forced to feed or starve. Bird repellents have been discussed in reviews (51,56). 

Several compounds may interfere with nucleic acid metabolism but commonly their effects are secondary to their primary mode of action, for example, the benzimidazoles. Compounds that inhibit nucleic acid biosynthesis directly are either phenylamides, pyrimidines or hydroxy-pyrimidines. Recently, the phenoxyquinolines were identified as exhibiting a novel mode of action in purine biosynthesis and are potentially useful fungicides. 

There are two commercial fungicides, the antibiotics blasticidin S and kasugamycin, that act via the inhibition of protein biosynthesis (Figure 4.19). Blasticidin S is a fermentation product obtained from cultures of Streptomyces griseochromogenes, and has specific activity in the control of P. oryzae, similar to kasugamycin, a secondary metabolite of S. kasugaensis. However, much of the earlier work on mode of action was carried out using another antibiotic, cycloheximide. 

Fig. 2). The staphylococcal enzyme may appear to be more akin in its mode of action to the spleen enzyme because they both hydrolyze DNA and RNA to 3 -nucleotides, whereas the venom enzyme releases 5 -nucleotides. However, their mode of action and specificity are quite different, and the structural requirements of the staphylococcal enzyme substrates are perhaps more nearly similar to those of the venom enzyme. The principal difference is that the staphylococcal enzyme cleaves the diester bond between the phosphate and the 5 -carbon of the sugar, whereas the venom enzyme cleaves on the other side of the phosphate, that is, between the phosphate and the nonspecific hydroxylic component of the diester bond. In contrast to both spleen and venom diesterases, the primary product released by staphylococcal nuclease hydrolysis is a derivative bearing a hydroxyl group (on the 5 position) rather than a phosphoryl group. Therefore, the 3 -phosphoryl product formed from polynucleotide hydrolysis is a secondary consequence of such cleavage. 

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