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The strong inhibition of Human Cytomegalovirus (HCMV) replication by benzimidazole nucleosides, like Triciribine and Maribavir, has prompted us to expand the structure-activity relationships of the benzimidazole series, using as a central core the imidazo[4,5-b]pyridine scafflold. We have thus synthesized a number of novel amino substituted imidazopyridine nucleoside derivatives, which can be considered as 4-(or 7)-aza-d-isosters of Maribavir and have evaluated their potential antiviral activity. The target compounds were synthesized upon glycosylation of suitably substituted 2-aminoimidazopyridines, which were prepared in six steps starting from 2-amino-6-chloropyridine. Even if the new compounds possessed only a slight structural modification when compared to the original drug, they were not endowed with interesting antiviral activity. Even so, three derivatives showed promising cytotoxic potential. © 2020 by the authors.

Some novel 1,3,4-thiadiazole [5-8] and 1,2,4-triazole [9-12] derivatives carrying amino acid moiety were synthesized starting from L-methionine. 1,3,4-Thiadiazole and 1,2,4-triazole scaffolds were prepared by cyclocondensation of the corresponding thiosemicarbazide and finally converted to their thiourea derivatives. Structures of the synthesized compounds [4-12] were confirmed by IR, 1H-NMR and 13C-NMR spectral data and elemental analysis. Synthesized compounds were evaluated for their antiviral and antibacterial activity. Of the screened compounds, N-{3-(methylsulfanyl)- 1-[5-(phenylamino)-1,3,4-thiadiazole-2-yl]propyl}benzamide [5] was identified as the most potent inhibitor of Influenza A H3N2 virus with an EC50 value of 31.4 µM, which serves as a lead compound for prospective development. The antituberculosis activity screen of the synthesized compounds revealed 1-[4-(4-chloro-(3-trifluoromethyl)phenyl]-3-[3-(methylsulfanyl)- 1-(4-phenyl-5-thioxo-4,5-dihydro-1H-1,2,4-triazole- 3-yl)propyl]thiourea [12] as the most active compound against M. tuberculosis H37Rv strain (MIC : 30.88 µM) but the compound proved not selective. © 2015, Marmara University. All rights reserved.

Осуществлен синтез серии производных урацила, содержащих в положении 3 пиримидинового цикла N-(4-феноксифенил)ацетамидный фрагмент, и изучена их противовирусная активность. Показано, что соединения этого ряда проявляют мощную ингибиторную активность в отношении цитомегаловируса человека (штаммы AD-169 и Davis) в культуре клеток HEL. Обнаружено, что некоторые соединения проявляют заметную активность в отношении вируса ветряной оспы-опоясывающего лишая (varicella zoster virus).

Orf virus, a member of the Parapoxvirus genus, causes a contagious pustular dermatitis in sheep, goats and humans. Previous studies have demonstrated the activity of [(S)-1-(3-hydroxy-2-phosphono-methoxypropyl)cytosine] (HPMPC, cidofovir, CDV, Vistide®) against Orf virus in cell culture (Nettleton et al., 2000, Antiviral Res., 48: 205-8) and in humans (Geerinck et al., 2001, J. Med. Virol. 64: 543-9). We evaluated a broad range of acyclic nucleoside phosphonates (ANPs) against several Orf virus strains in primary lamb keratinocytes (PLK) and human embryonic lung (HEL) monolayers. The activity of the ANPs was higher in HEL than in PLK cells: the EC50 values for HPMPC were in the range of 0.1-0.8 Ìg/ml and 0.2-3.5 Ìg/ml in HEL and PLK, respectively; (S)-9-(3-hydroxy-2-phosphonomethoxy-propyl)-2,6-diaminopurine (HPMPDAP) was active at 0.08 to 0.1 Ìg/ml in HEL and at 0.1 to 3.2 Ìg/ml in PLK. The activity of HPMPC, HPMPDAP and (S)-9-(3-hydroxy-2-(phosphonomethoxy-propoxy)-2,4-diaminopyrimidine (HPMPO-DAPY) was confirmed by virus titration and DNA quantification at different time points in both cell lines. HPMPC, HPMPDAP and HPMPO-DAPY were evaluated for their activity against Orf virus replication in organotypic epithelial raft cultures from differentiated PLK cells. At the highest concentrations (50 and 20 Ìg/ml), a full protection was provided by the three drugs, while at 5 Ìg/ml only HPMPDAP and HPMPC offered partial protection. These findings confirm the activity of HPMPC and other ANPs against Orf virus and provide a rationale for their use in the treatment of orf (contagious ecthyma) in humans and animals.

The new thiosemicarbazones and thiocarbonohydrazones 4a-d, 5a-d derived from 2-(1-adamantylcarbonyl)pyridine and 1-acetyladamantane were synthesized and evaluated for their inhibitory effect on tumor cell proliferation and their antiviral and antimicrobial activity. Thiosemicarbazone 4a inhibited tumor cell proliferation (GI50's range: 2.4-100 μM and mean GI50 43.9 μM against various human leukemic cell lines) while thiosemicarbazone 5a and thiocarbonohydrazone 5d exhibited significant inhibition of tumor cell proliferation (GI50's range 2.3-23.6 μM and mean GI50 7.2 μM for 5a and GI50's range 2.4-32.4 μM and mean GI50 12.8 μM for 5d). These GI50 values are comparable to that of 2-acetylpyridine thiosemicarbazone an important lead in TSC's family. The compounds did not afford specific activity against any of the viruses tested when examined at non-toxic concentrations. A weak activity was found for thiocarbonohydrazones 4d, 5d against Gram-(+) bacteria (MIC50 117.3 and 133 μM, respectively). Using a combination of molecular mechanics calculations and NOE spectroscopy it was shown that the parent compounds 4a and 5a have opposite configuration around C=N bond. Whether this difference in structure can be correlated with the biological activity will be investigated in future studies. © 2002 Elsevier Science Ltd. All rights reserved.