Antiviral screening

The extracts of T. affinis, T. arborea, T. divaricata, T. heyrteana, and T. pandacaqui showed some degree of antitumor activity, whereas the extracts of T. malaccensis, T. dichotoma, and T. crassa exhibited hypotensive effects (9). Recently a systematic antimicrobial, antiamoebic, and antiviral screening of 19 different Tabernaemontana species has been carried out with positive results (218). 

Richter et al. prepared /V-benzoyl-/V -(/V-aryloxamoyl) ureas 138 (R = Ph R = H, Me) by using a sequence of reactions involving ben-zoylation, reaction with oxalyl chloride, and, finally, reaction with anilines (Scheme 5) (78JOC4150). Karparov et al. found, in broad-spectrum antiviral screening, that Mannich bases 139 (m = 4,5) showed some activity, but that the parent urea (104) and thiourea (105) did not (84AF9). However, a later study revealed the two Mannich bases were inactive toward alphavi-rus models (86MI1). 

The well known spirostane triglycosides 45 dioscin and 46 gracillin, which have diosgenin as aglycone, are cytotoxic above 4 and 20 pg/ml respectively, and do not give interesting results below these concentrations in the antiviral screenings (Table 9) (32). 

The literature on antiviral screening for HHV-6 and HHV-7 is sparse and has been reviewed elsewhere (1,3-5). Cell systems for viral propagation have included primary human peripheral blood and cord blood lymphocytes (CBL), and T-cell lines. Methods for monitoring viral replication have included examining infected cultures for cytopathic effect, immunofluorescence analysis, quantitation of viral DNA, and focus-forming assays. Phosphonoformic acid (foscarnet), phosphonoacetic acid, and ganciclovir inhibit HHV-6 and HHV-7... 

Table 3. Result of Antiviral Screening of Buchettavia Alkaloids...

Infectious virus diseases remain an important worldwide problem due to the nature of these infectious agents, which totally depend upon the cell that they infect for their multiplication and survival. This characteristic has made development of effective chemotherapeutic agents for treatment of viral infections very difficult, and as a consequence there are only a few antiviral drugs available for the cure of vims diseases. During the last years, the search for natural compounds with antiviral activity has been intensified. Antiviral screening programmes of indigenous medicinal plants are very important, not... 

Four basic approaches are conducted for plant selection for antiviral screening assays 1- Random collection of plants followed by mass screening. 2- Ethnomedical approach. 3- Literature-based follow up of the existing leads. 4- Chemotaxonomic approach [12]. The second and third approaches are the most favored ones because of their cost-effective applicability. The selection based on folkloric use proved five times higher percentage of active leads than other approaches. The random approach usually affords more novel compounds with antiviral activity. Combining ethnomedical, phytochemical and taxonomical approaches is considered the best compromise. 

These biochemical and antiviral screening studies (10,12-16) suggest that FEAU should be more selective in its antiviral activity and thus offer less host toxicity. In vivo experiments in mice (10.13) show that both FMAU and FEAU are relatively nontoxic. However, FMAU is very nenrotoxic in dogs (lethal dose 2.5 mg/kg/day, i.v. x S), while preliminary studies on FEAU in dogs at 50 mg/kg/day x 10 show no encephalopathy (lethal dose 100 mg/kg/day x 10). As mentioned previously, FMAU exhibited dose-limiting CNS toxicity in patients with advanced cancer (2) at an intravenous dose of 0.8 mg/kg/day x 5. The toxicity of FEAU in humans is not known. 

McCutcheon AR, Roberts TE, Gibbons E et al (1995) Antiviral screening of British Columbian medicinal plants. J Ethnopharmacol 49 101-110... 

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