Antiviral activity in cell cultures

Scheme 7 Microwave methods for preparation of C2-symmetric HIV-1 protease inhibitors modified in Pl/Pl, enzyme inhibition, and antiviral activity in cell culture...

The symmetrical seven-membered sulfone, 11 (Table I), has been reported by Kim to show high in vitro potency (IC50 = 1 nM), good antiviral activity in cell culture (EC90 = 20 nJM), and excellent pharma-... 

One feature of the hydroxypyranones that presented a major challenge was the poor translation of high intrinsic inhibitory potency against the enzyme into antiviral activity in cell culture (Prasad et al., 1996). The acidic character of the enolic hydroxy group (pAa 4.2-6.5) as compared with aliphatic hydroxyl groups found in other classes of inhibitors did not appear to offer an explanation in as much as inhibitors of the pyranone class penetrate cells efficiently (Vara Prasad et al, 1995). Empirically,... 

Testing Compounds for Antiviral Activity in Cell Cultures Infected with HIV... 

Although the phthalimido-bearing pyridinone 1 (Figure 41.4) is a potent reverse transcriptase inhibitor (/C50 = 30 nM), hydrolytic instability under physiological conditions precludes the demonstration of its antiviral activity in cell culture. This instability was recognized to be due to the aminal structure of the exocyclic NH. 

Most animal viruses are inhibited by IFNs, although many DNA viruses are relatively iuseusitive. Cousiderable differeuces iu seusitivity to the effects of IFNs exist amoug differeut viruses and assay systems. The biological activity of IFN usually is measured iu terms of antiviral effects in cell culture and generally is expressed as international units (IU) relative to reference standards. 

Kiritsis et synthesised a new series of pyrimidine pyranonucleo-sides (31). These compounds have a cyano group on the pyranose moiety which results in a significant change in biological activity and physical properties. The synthesised compounds with cyano substitution showed antiviral and cytostatic activities in cell culture. 

Novel isosteres 545 of the antiviral agent acyclovir were synthesized in three stages (84JHC697) by dehydrative coupling of 3-amino-6-aminomethyl[ 1,2,4]triazin-5-(4//)-one with 2-(benzoyloxy)ethoxyacetic acid to give the respective amide that cyclized and deprotected to give 545. It showed no activity against herpes simplex virus types I and II in cell culture (Scheme 112). 

However, the nucleoside analogue 164 was found to be devoid of activity against HSV-1, HSV-2, VZV and the cytomegalovirus (CMV) in human fibroblast (MRC-5) cells. In this case the decreased conformational flexibility resulting from the introduction of the cyclopropyl group into 164 appeared to be unfavourable for interaction with the enzymes involved (vide supra. Sect. 2.9) [222]. Likewise, the cyclopropylpyrimidine 166c-f and 167, the cyclopropyl-purine nucleosides 168 showed no antiviral activity against HSV-1, HSV-2, HCMV and HIV-1 in cell culture, Eq. (66) [223]. 

Pharmacology Valacyclovir is the hydrochloride salt of L-valyl ester of the antiviral drug acyclovir. Valacyclovir is rapidly converted to acyclovir, which has in vitro and in vivo inhibitory activity against herpes simplex virus types I (HSV-1) and II (HSV-2), and varicella-zoster virus (VZV). In cell culture, acyclovir has the highest antiviral activity against HSV-1, followed by (in decreasing order of potency) HSV-2 and VZV. In vitro, acyclovir triphosphate stops replication of herpes viral DMA in 3 ways 1) Competitive inhibition of viral DMA polymerase 2) incorporation and termination of... 

Antiviral activity. Hot water extract of the seed, in cell culture, produced weak activity on poliovirus 1 ... 

Antiviral activity. Water extract of the dried fruit, in cell culture at a concentration of 10%, was inactive on herpes virus-type 2, influenza, poliovirus, and vaccina . Tincture of the dried fruit, administered orally to adults of both sexes at a dose of 60 mL/person, was active on herpes virus. PCT patent number W096/14064 reported treatment of six subjects with herpes virus infections. The activity was highly dose... 

Antiviral activity. Ethanol (80%) extract of the dried leaf, in cell culture at a concentration of 0.2 mL/well, was equivocal on poliovims inactive on herpes virus, measles, and Semliki Forest virus and produced weak activity on coxsackie virus Pretreatment of mice with sesame extract failed to reduce the cytophatic effect of human immunodeficiency virus 1 (HlV-1) infection in MT-4 cells. No apparent acute toxicity was detected in mice with oral administration of 10 g/kg of the extract "". ... 

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