Structural characteristics were identified that may contribute to the understanding of the larvicidal activity of phenylpropanoids. The present approach may help future work in the search for larvicidal compounds.

Nucleoside analogues have been the cornerstone of antiviral therapy over the past thirty years and, currently, 16 commonly used antiviral drugs belong to this category. Although for long time it was believed that only D-nucleosides, possessing a 'natural' stereochemistry, could elicit biological activity, in the last decade this has been proven not to be true. 3TC, a L-nucleoside analogue, is one of the most effective anti-HIV and anti-hepatitis B virus drugs, and nine other L-nucleosides are currently undergoing clinical trials and/or preclinical studies as antiviral or antitumoral agents. This minireview summarizes some biological features and the current status of these promising L-nucleoside analogues.

Our recent studies demonstrated that d- and l-2'-fluoro-2',3'-unsaturated nucleosides (d- and l-2'-F-d4Ns) display moderate to potent antiviral activities against HIV-1 and HBV. As an extension of these findings, beta-d-3'-fluoro-2',3'-unsaturated nucleosides were synthesized as potential antiviral agents. The key intermediate (2S)-5-(1,3-dioxolan)-1-benzoyloxy-3,3-difluoropentan-2-ol 6 was prepared from 2,3-O-isopropylidene-d-glyceraldehyde 1, which was converted to 5-O-benzoxy-d-2-deoxy-3,3-difluoropentofuranosyl acetate 7 by the ring-closure reaction under acidic conditions. The acetate 7 was condensed with silylated purine and pyrimidine bases, which produced the alpha and beta isomers. The 3',3'-difluoro nucleosides were then treated with t-BuOK to give the desired 3'-fluoro-unsaturated nucleosides. We studied the structure-activity relationships of d-3'-fluoro-2',3'-unsaturated nucleosides against HIV-1 in human peripheral blood mononuclear cells, from which we found that the cytosine derivative 26 was the most potent among the synthesized compounds. To understand the mode of action and drug resistance profile, with particular regard to the role of fluorine, we performed the molecular modeling studies of the cytidine analogue d-3'F-d4C and found a good correlation between calculated relative binding energies and activity/resistance data. Our model also shows interactions of the 3'-fluorine and the 2',3' double bond, which can be correlated to the observed biological data. Differences between fluorine substitution at the 3' and 2' positions may account for the higher cross-resistance with lamivudine observed in the 2'-fluorinated series.

As one of the earliest developed antimicrobial classes, sulfonamides remain important therapeutic options for the empiric and definitive treatment of various infectious diseases. In the general population, approximately 3–8% of patients are reported to experience a sulfonamide allergy. Sulfonamide allergies can result in various physical manifestations; however, rash is reported as the most frequently observed. In patients with human immunodeficiency virus (HIV), dermatologic reactions to sulfonamide antimicrobial agents occur 10 to 20 times more frequently compared to immunocompetent patients. This article describes the incidence, manifestations, and risk factors associated with sulfonamide allergies. The potential for cross-reactivity of allergies to sulfonamide antimicrobials with nonantimicrobial sulfonamide medications is also reviewed. Data suggest that substitutions at the N1 and N4 positions are the primary determinants of drug allergy instead of the common sulfonamide moiety. For patients with an indication for a sulfonamide antimicrobial with a listed allergy, it is important for healthcare practitioners to adequately assess the allergic reaction to determine appropriate management. Rechallenge and desensitization strategies may be appropriate for patients with delayed maculopapular eruptions, while alternative treatment options may be prudent for more severe reactions. Available data suggests a low risk of cross-allergenicity between sulfonamide antimicrobial and nonantimicrobial agents.