Chemical composition of Propolis Extract ACF® and activity against herpes simplex virus.

UNLABELLED: Propolis Extract ACF(®) (PPE) is a purified extract manufactured from propolis collected in a Canadian region rich in poplar trees, and it is the active substance of a topical ointment used against herpes labialis (cold sores or fever blisters). Aim of this study was to analyze the chemical composition of PPE in order to understand the plant origin and possible relations between compounds and antiviral activity, and to characterize the antiviral activity of the extract against herpes simplex virus in vitro. MATERIAL AND METHODS: The analysis of the propolis extract samples was conducted by Gas Chromatography-Mass Spectrometry (GC-MS). The antiviral activity was tested against herpes simplex viruses type 1 and type 2 in MDBK cell cultures by treating the cells with PPE at the time of virus adsorption, and by incubating the virus with the extract before infection (virucidal assay). RESULTS: Results from the GC-MS analyses revealed a dual plant origin of PPE, with components derived from resins of two different species of poplar. The chemical composition appeared standardized between extract samples and was also reproduced in the sample of topical ointment. The antiviral studies showed that PPE had a pronounced virucidal effect against herpes simplex viruses type 1 and type 2, and also interfered with virus adsorption.

Transformation of cholanic acid derivatives into pharmacologically active esters of phenolic acids by heterogeneous Wittig reaction.

Steroid esters of cynnamic acid derivatives have been synthesized by a heterogeneous Wittig reaction under sonochemical conditions from the corresponding triphenylphosphonium bromides and unprotected phenolic aldehyds using K2CO3 as a base. 5 beta-Cholan-3 alpha, 7 alpha, 12 alpha, 24-E-ferulate (11') exhibited a marked inhibitory effect on influenza virus A. The synthetic 3 alpha, 24-E-diferulates of 5 beta-cholan-3 alpha, 24- diol, 5 beta-cholan-3 alpha, 12 alpha, 24-triol and 5 beta-cholan-3 alpha, 7 alpha, 12 alpha, 24-tetrol (8, 9 and 12) showed antitumor activity on leukemia P-388 in mice.

Antiviral activity of some hydroxycoumarin derivatives.

Esculetin (6,7-dihydroxycoumarin) and its diacetate exhibited a marked inhibitory effect on Newcastle disease virus replication in cell cultures at concentrations of 36 microM and 62 microM, respectively. These compounds were selected from ten hydroxycoumarin derivatives through an in vitro antiviral screen involving viruses of the picorna-, orthomyxo-, paramyxo-, and herpes virus families.

Thiourea derivatives as specific inhibitors of picorna viruses.

30 compounds with antipicorna virus activity were selected from 173 N,N'-disubstituted thiourea derivatives. The spectrum of antiviral activity was determined in vitro using entero, FMD, rhino and EMC viruses. Structure-activity relationships were studied. Several compounds produced marked activity against coxsackie viruses A and B infection of mice and FMD infection in mice and guinea pigs. N-Phenyl-N'-3-hydroxyphenyl-thiourea (PTU-23) inhibited poliovirus production by more than 99% without influencing the FL host cell. EMC virus was readily inhibited by PTU-23 in Kreb-II cells. Virus RNA synthesis was significantly reduced. Under the effect of PTU-23 the amount of 37S ssRNA extracted from EMC virus infected cells was considerably more reduced than that of the 20S ds RNA. PTU-23 did not influence the activity of virus-induced RNA polymerase in a cell-free system.

Methodical aspects of the experimental chemotherapy of viral infections.

An analysis of the methods of testing the antiviral activity in vitro (in cell cultures) and in vivo (in experimental virus infections) is presented. The necessity of applying two-stage screening in vitro is emphasized. The chemotherapeutic viral models is in vitro testing as well as the principles of modelling of experimental viral infections are examined. Criteria for stage-by-stage assessment of the antiviral activity of the substances tested are formulated.

Antirival activity of N-phenyl-N'-arylthiourea derivatives against some Rhinoviruses.

The effect of 12 derivatives of N-phenyl-N'-aryl- or alkylthiourea, inhibitors of human enteroviruses and foot-and-mouth disease virus, on reproduction of some rhinoviruses (H-17, B-632) in HeLa Bristol cells was studied. As screening methods both the multicylce growth test in roller tube cultures and two variants of plaque inhibition tests were employed. The compounds selected were tested in one-step growth cycle set-up. We established that N-phenyl-N'-4-hydroxyphenylthiourea (V-24) and N-phenyl-N'-2-carboxyphenylthiourea (V-17) have a distinct inhibitory effect on the growth of rhinovirus H-17, and N-phenyl-N'-2-hydroxy-5-nitrophenylthiourea (V-25) inhibited strongly the multiplication of rhinovirus B-632.

On the structure-activity relationship of antiviral substances.

The significance of the study on structure-activity relationship in the antiviral substances is considered for: 1. directed synthesis of highly active and selective antivirals; 2. elucidation of the mechanism of action of antiviral substances by revealing the chemical structures which determine the inhibition of a given step in the virus growth cycle. The basic trends in conducting directed synthesis of antiviral substances are pointed out: synthesis of new inhibitors with a broad antiviral spectrum, as well as improvement by structural modifications of known ones. The basic methodological approaches in the structure-activity studies are considered. A classification of the available antiviral synthetic substances is presented.

Antiviral activity of N-phenyl-N'-aryl- or alkylthiourea derivatives in Coxsackie virus infections in mice.

The effect of five derivatives of N-phenyl-N'-aryl- or alkylthiourea-inhibitors of the multiplication of Coxsackie virus B1 and other picornaviruses in vitro-was tested in experimental infections with Coxsackie viruses B1, B3, A6, and A7 in newborn mice. Under the action of N-phenyl-N'-3-hydroxyphenylthiourea (no. 23) and N-phenyl-N'-4-carboxy-5-hydroxyphenylthiourea (no. 20) a two- to threefold reduction in mortality was observed, as well as an appreciable delay in the course of the disease (mean effective dose, lengthening by 2 to 6 days) after infection with Coxsackie viruses B1, B3, and A7. The infection with Coxsackie virus A6 was affected only by compound no. 23 and, at that, to a low degree. If the antiviral effect is to be obtained, the compounds must be applied daily (once subcutaneously) from the 24th to the 144th h after virus inoculation, a period which corresponds to the incubation period and the beginning of the manifested infection. On the basis of these data, as well as of the relatively high selectivity (therapeutic index of 3 to 20), the two indicated substances may be considered to be reliable antiviral chemotherapeutic agents.