Adenoviral infection is a serious human pathology leading to respiratory, gastrointestinal and ocular disorders and epidemic outbreaks, especially in children's groups. Here we present the results from an investigation of anti- adenoviral effect of 6-azacytidine (6-AC) both in vitro and in vivo. The selectivity index of 6-AC for adenovirus type 5 in HEp-2 cells was 374, the 50% effective concentration was 0.5 mg/ml. For in vivo investigations we developed a model of disseminated adenoviral infection in newborn Syrian hamsters. The infectious virus was recovered from the liver, kidney, lungs and heart. Application of 6-AC led to a reduced period of the virus presence (7 days in the liver and 4 days in the kidney and heart) and lowered virus titers on day 3 post-inoculation (p.i.) (liver - 2.7 and 4.1, heart - 0 and 3.2, kidney - 0 and 2.4 log(10 )CPD(50)/mg tissue weight, in the presence and absence of 6-AC, respectively). Application of 6-AC to newborn Syrian hamsters led to partial destruction of their splenocytes. The results obtained suggest that 6-AC or 6-ACbased drugs with lower toxicity or applied topically may be suitable for therapy and prevention of adenoviral infection in humans.

Influenza remains a highly pathogenic and hardly controlled human infection. The ability of selecting drug-resistant variants necessitates the search and development of novel anti-influenza drugs. Herein, we describe the synthesis and evaluation of a series of novel 2-substituted 7,8-dihydro-6H-imidazo[2,1-b][1,3]benzothiazol-5-ones 3a-k for their virus-inhibiting activity against influenza A virus. The new analogues 3a-k prepared in two steps from commercially available cyclohexane-1,3-diones were fully characterized by their NMR and mass spectral data. Among the new derivatives screened for cytotoxicity and in vitro antiviral activity against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cells, three analogues 3i-k containing a thiophene unit were found to exhibit high virus-inhibiting activity (high SI values) and a favorable toxicity profile. The compound 3j (CC 50 : >1000 μM, SI = 77) with higher potency is the best anti-influenza hit analogue for further structural optimization and drug development. The most active compounds did not inhibit viral neuraminidase and possess therefore other targets and mechanisms of activity than the currently used neuraminidase inhibitors.

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Here we report a reaction of the fullerene derivatives C60Ar5Cl, which enables the substitution of Cl with thiophene residues and the formation of the novel family of C 1-symmetrical C60 fullerene derivatives with six functional addends C60Ar5Th. The discovered reaction provided a straightforward approach to the synthesis of previously inaccessible multifunctional water-soluble fullerene derivatives, including the compounds with antiviral activity against human immunodeficiency and influenza viruses.

The antiviral activity of several amides and thio-and carboxamides of ()-cytisine in addition to bromination and nitration products of its 2-pyridone core was studied. Compounds with a selectivity index close to 10 were found.Keywords: ()-cytisine, H1N1 flu virus.Some plants that exhibit antiviral properties are known to bear alkaloids. Thus, several genera of the family Fabaceae, e.g., Sophora, Acacia, and Caragana, yield extracts that are highly active against hepatitis C (HCV), hepatitis B (HBV), Herpes simplex 1 (HSV-1), and several other viruses [1][2][3][4][5].The search for new antiviral agents should be conducted among representatives of the most common structural groups of quinolizidine alkaloids, including ()-cytisine, because plants of the family Fabaceae are the principal producers of them [6] and the aforementioned antiviral properties may be associated with them.The pharmacological profiles of ()-cytisine itself and its derivatives are very broad. Neuropharmacological, antiinflammatory, analeptic, and antidiabetic activity was established for them [7]. An example of a study of the antiviral properties of ()-cytisine itself and several of its synthetic derivatives was published [8].We synthesized two groups of derivatives of ()-cytisine and N-methylcytisine that contained substituents on the secondary N atom and in the 2-pyridone core in order to discover compounds with antiviral activity and to establish the structure-activity relationship.The transformation products of the ()-cytisine secondary amine were amides of m-fluoro-, m-bromo-, and p-chlorobenzoic acids (1-3) that were prepared by the hydroxysuccinimide method as before [9]. The syntheses of thio-and carboxamides 4 and 5, substituted ureas 6 and 7, nitro derivatives 9 and 10, carbamide 12, and dibromo derivative 8 were described by us previously [10,11]. Dinitro derivative 11 was synthesized by repeated nitration of 9. Table 1 summarizes results from the study of the toxicity and antiviral activity of cytisine derivatives 1-12. According to the results, starting alkaloid ()-cytisine had low toxicity and antiviral activity. Transformation products of the ()-cytisine secondary amine, i.e., amides of m-fluoro-, m-bromo-, and p-chlorobenzoic acids 1-3, differed in toxicity and activity. This indicated that the nature of the corresponding acid and the halogen atom and its position on the aromatic ring affected the antiviral properties.