Halogenated isoniazid derivatives .6. Evaluation of anti-HSV-1 and anti-HIV-1 in vitro activities of fluorinated analogues

The synthesis and evaluation of antiviral in vitro activity are reported of some 2'-(1-arylethyl)isonicotinohydrazides (5a-d) and N-(1-arylethyl)isonicotinohydrazonic acids (6a-d), obtained by reducing fluorinated acetophenone isonicotinoylhydrazones (2a-d) with sodium cyanoborohydride. These INH analogues, along with other ones previously prepared, i.e. benzaldehyde isonicotinoylhydrazones 1, 4-aryl-1-methoxy-1-(4-pyridyl)-2,3-diaza-1,3-butadienes 3 and 5-aryl-4-methyl-2-(4-pyridyl)-Δ2-1,3,4-oxadiazolines 4, were assayed for anti-HSV-1 activity on the monoblastoid cell line U937. Only some compounds (1b, 1d, 4d and 4e) displayed a moderate antiherpetic activity. In addition, the reduced compounds 5 and 6, submitted to the anti-HIV-1 screening, did not display significant effects in reducing virus-induced cythopathogenicity. The cytotoxicity of all compounds has been assayed on Vero cells and some considerations in correlation with structure are discussed.