Antiviral activity of FA-11H on the infectivity and replication of herpes simplex virus type 1 in cultured cells.

The highest concentration lacking cytotoxicity (h.c.l.c.) of the acid FA-11H, related to ester FA-11 (ethyl 4-trifluoromethyl-2-methylthio-5-pyrimidinecarboxylate), was determined on Vero cultured cells. At this concentration (300 micrograms/ml) FA-11H produced an 81.4% inhibition of herpes simplex virus type 1 infectivity with respect to the plaque formation detected in control infected cultures. This inhibitory activity was substantiated by studies on progeny production. FA-11H revealed a higher therapeutic index than that of the related ester FA-11. However, the therapeutic index of FA-11H appeared to be lower than that of its potassium salt. These results indicate that the presence of potassium ions could facilitate the internalization and therefore the antiviral activity of the anions corresponding to analysed compound.

Evaluation of the trophic effect of human placental polydeoxyribonucleotide on human knee skin fibroblasts in primary culture.

A simple assay capable of evaluating the trophic effect of growth factors or active principles on human skin diploid fibroblasts in primary culture has been developed. The results indicate that at physiological concentrations (20-100 micrograms/ml) a human placental polydeoxyribonucleotide (PDRN) preparation enhances the growth of human skin diploid fibroblasts of the knee in primary culture. This effect is consistently reproducible in the case of patients over 60 years of age, and may explain previously reported data on the successful clinical applications of human placental preparations, suggesting a selective benefit of PDRN in wound healing when compared to other treatments.

A short-term plaque assay for antiviral drug research on herpes simplex virus type 2.

In antiviral drug research, gelatinized growth medium cannot be used after infection to avoid the development of secondary plaques, because agar or other chemicals may interfere with the assessment of cytotoxic activity of antiviral compounds. In this study we evaluated quantitatively the different expression of cytopathic effects of Herpes Simplex Virus type 2 (HSV-2) in Vero cell cultures utilizing different periods of incubation after infection, and analysed the incidence of viral progeny particles on the formation of satellite plaques in order to define a short-term plaque assay utilizing a single cycle of infection. The results shown in the work suggest using a period of 24 hours of incubation post adsorption for a screening on inhibition of HSV-2 infectivity in antiviral drug studies.

Antiviral activity of S-7HNa on the infectivity and replication of herpes simplex virus type 1 in cultured cells.

The effect of sodium salt of the acid related to ester S-7 (i.e. S-7HNa) on the infectivity and replication of herpes simplex virus type 1 in Vero cultured cells was studied. S-7HNa, at the highest concentration lacking cytotoxicity (10 mM), produced, at various inocula, a 70% inhibition of HSV-1 infectivity with respect to the plaque formation detected in control infected cultures. This inhibitory activity was substantiated by studies on progeny production. S-7HNa revealed a therapeutic index higher than that of the correlative ester (S-7).

The mixed leukocyte reaction may promote the growth of human pericorneal fibroblasts in primary culture.

Keratitis of the cornea is believed to be the leading cause of loss of vision due to external eye disease in the United States and in Europe. At present, primary and secondary cell cultures obtained from corneal explants are the most suitable system to study the role of drug-resistant viruses in severe recurrences of infections leading to irreversible corneal scarring. In this work, the growth of human pericorneal fibroblasts in primary and secondary cultures has been obtained by cocultivation with a mixed leukocyte reaction.

Synthesis and antimicrobial activity of arylazoenamines.

The possibility to obtain new arylazoenamines endowed with antifungal activity was examined by reacting with acids the arylhydrazones of several keto- and aldo-tert, amines as dimethyl-3-aminoacetone, 3-quinuclidinone, 1-methyl-3-piperidone and 2-formyl-1-methylpyrrolidine. The reaction was successful only in the last two cases. From each 1-methyl-3-piperidone arylhydrazone two isomeric arylazoenamines were formed, which were identical with those obtained from the analogous arylhydrazone of 2-formyl-1-methylpyrrolidine. The structure of these compounds was settled on the ground of UV, IR, NMR and mass spectra and confirmed by means of X-ray analysis. A mechanism is proposed for the formation of arylazoenamines through the contraction of piperidine ring and enlargement of the pyrrolidinic one. The prepared compounds [3-arylazo-1-methyl-delta 2-piperideines 17 and 1-methyl-2(arylazo)methylene pyrrolidines 18 exhibited only a very weak antibacterial activity, but were moderately active against several Candida species and other yeast-like fungi.

S-7 inhibition of Herpes simplex virus type 1 infectivity and replication in cultured cells.

The effect of ethyl 2-methylthio-4-methyl-5-pyrimidine, carboxylate (S-7) on the infectivity and replication of herpes simplex virus type 1 in Vero cells was studied. S-7, at the highest concentration lacking toxic effect on cells (40 microg/ml), produced, at various inocula, a 40% inhibition of HSV-1 infectivity with respect to the plaque formation detected in control infected cultures. This inhibitory activity was substantiated by studies on progeny production. We cannot conclude that the inhibition of viral cytopathic effect resides in a specific inhibition of viral enzymes, however, the possibility of a more specific antiviral effect cannot be totally ruled out.

alpha-(1H-imidazol-1-ylmethylene)ketones with antimycotic activity.

A series of title compounds were synthesized starting from heterocyclic alpha-hydroxymethyleneketones and 1,1'-carbonyldiimidazole and tested against gram-positive and gram-negative bacteria, as well as fungi. 7,8-Dihydro-6-(1H-imidazol-1-ylmethylene)-2-phenylquinazolin -5(6H)-one showed a remarkable activity against Candida krusei.

[Quinolizidine derivatives with antibacterial activity]. / Derivati chinolizidinici ad attività antibatterica.

Six quinolizidinyl-derivatives were tested for antibacterial actvity against a large number of gram-positive and gram-negative strains. 9-Lupinyliden-fluorene (I) and its epimer (II) at concentrations between 12,5 and 100 mg/l inhibit all gram-positive strains, while they are only weakly active against a few gram-negative bacteria. The tertiary alcohols (III) and (IV) are inactive against the gram-positive strains, while still exhibiting weak activity on the gram-negative. Compounds (V) and (VI) are completely inactive. The values of minimal bactericidal concentrations for compound (I) against the sensitive strains are equal to or no more than 4 times higher than values of MIC. It is interesting to note that compound (I) is able to give rise to cellular lysis at MIC.