Inhibitory activity action mechanism

The mode of action of PMEA may be quite similar to the mechanism by which (3)-HPMPA accomplishes its selective inhibitory activity against herpes vimses. Eor PMEA to reach its active triphosphate form, it needs only two phosphorylation steps. The triphosphate derivative of PMEA has a much stronger affinity for HIV-1 reverse transcriptase than for cellular DNA polymerases (175). Whether it is actually incorporated into DNA and terminates the growing DNA chain is currentiy under investigation. 

After clavulanic acid, the penicillanic acid derivatives (particularly the corresponding sulfone analogs) have been the subject of intense research in the -lactamase inhibitor area. From this extensive investigation, two compounds (sulbactam and tazobactam) from this class have been successfully introduced into clinical use. The penicillanic acid sulfones are /3-laclamasc inhibitors that are quite homologous to clavulanate in both their mechanism of action and in the spectrum of -lactamases susceptible to their action. The first notable success in this field was the discovery of sulbactam 7 (Fig. 7), which was reported by Pfizer chemists in 1978 and shown to possess potent inhibitory activity, principally for class A //-lactamases. It had greater affinity for class C types than clavulanate. From careful comparison of its structure to clavulanate, a rational basis for the similarities between the two is apparent. Both lack a C-6 substituent. Since the absence (or presence) of this substituent is an important, but not exclusive, factor in //-lactamase recogni-... 

The mechanism of action of valproate is complex and still the subject of uncertainty. The drug appears to act by enhancing GABAergic function. Thus it increases GABA release, inhibits catabolism and increases the density of GABA-B receptors in the brain. There is also evidence that it increases the sensitivity of GABA receptors to the action of the inhibitory transmitter. Other actions that may contribute to its therapeutic effects include a decrease in dopamine turnover, a decrease in the activity of the NMDA-glutamate receptors and also a decrease in the concentration of... 

Ribavirin is a synthetic guanosine analogue that possesses broad antiviral inhibitory activity against many viruses, including influenza A and B, parainfluenza, RS V, HCV, HIV-1, and various herpesviruses, arenaviruses, and paramyxoviruses. Its exact mechanism of action has not been fully elucidated however, it appears to inhibit the synthesis of viral mRNA through an effect on nucleotide pools. Following absorption, host cell enzymes convert ribavirin to its monophosphate, diphosphate, and triphosphate forms. Ribavirin monophosphate... 

Mechanism of Action Penciclovir triphosphate inhibits HSV polymerase competitively with deoxyguanosine triphosphate. Consequently, herpes viral DNA synthesis and, therefore, replication are selectively inhibited. Therapeutic Effect An antiviral compound that has inhibitory activity against herpes simplex virus types 1 (HSV-1)... 

Keskin O, Bahar I, Jernigan RL et al. Characterization of anti-cancer agents by their growth inhibitory activity and relationships to mechanism of action and structure. Anti-Cancer Drug Design 2000 15 79-98. 

Acyclovir, valacyclovir, penciclovir, and famciclovir are synthetic guanine analogs with inhibitory activity against members of the herpesvirus family, including herpes simplex types 1 and 2. Their mechanism of action, indications, and usage in the treatment of cutaneous infections are discussed in Chapter 49. 

Mechanism of Action of Florfenicol. The inhibitory activities of chloramphenicol (1, R = NCh). thiamphenicol (1, R = SO2CH3), and florfenicol (2) against a sensitive E cofi strain have been studied. In two different liquid media, both chloramphenicol and florfenicol allowed only 20-30% residual growth at a drug concentration of 2 mg/L, whereas a thiaiuplieiiicul concentration of 25 mg/L was required to produce a similar effect. Florfenicol was also found to be a selective inhibitor of prokaryotic cells. At concentrations of 1 mg/L chloramphenicol and florfenicol, and at a concentration of 25 mg/L, thiamphenicol, inhibited protein synthesis. 

Whatever the mechanism of action for the inhibition of 5-lipoxygenase by flavonoids, it appears to be distinct from the antioxidant properties of these compounds. The results comparing antioxidant activity with leukotriene inhibitory activity clearly demonstrate this distinction. The profound effects of metabolic transformation on the anti-inflammation activity of dietary flavonoids such as quercetin must also be considered in relation to in vitro studies, and further highlights the need to use actual metabolic forms of flavonoids rather than the free aglycone or glycosides occurring in the diet. 

FIGURE 21.4 Possible mechanism for the action of ligand-regulated aptamers. (a) Addition of the ligand inhibits aptamer function and promotes the dissociation of the aptamer-receptor complex, (b) Addition of the ligand induces formation of the aptamer-receptor complex and activates aptamer function. Inhibitory activity of aptamers is assumed in both cases. L Ligand that controls aptamer activity A inactive aptamer A active aptamer R receptor (aptamer target). 

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