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[Display omitted] • Design, synthesis and evaluation of a new library based on 3-amino-1,2-propanediol skeleton. • Nitrogen was functionalized as phenyl urea and hydroxyl groups as substituted benzoyl esters or triazoles. • Seven compounds showed high anti-HAdV activity (IC 50 2.47–5.75 µM) and low cytotoxicity. • Predicted mechanisms of action involve different steps on the HAdV replicative cycle. Nowadays there is not an effective drug for the treatment of infections caused by human adenovirus (HAdV) which supposes a clinical challenge, especially for paediatric and immunosuppressed patients. Here, we describe the design, synthesis and biological evaluation as anti-adenovirus agents of a new library (57 compounds) of diester, monoester and triazole derivatives based on 3-amino-1,2-propanediol skeleton. Seven compounds (17 , 20 , 26 , 34 , 44 , 60 and 66) were selected based on their high anti-HAdV activity at low micromolar concentration (IC 50 from 2.47 to 5.75 µM) and low cytotoxicity (CC 50 from 28.70 to >200 µM). In addition, our mechanistic assays revealed that compounds 20 and 44 might be targeting specifically the HAdV DNA replication process, and compound 66 would be targeting HAdV E1A mRNA transcription. For compounds 17 , 20 , 34 and 60 , the mechanism of action seems to be associated with later steps after HAdV DNA replication. [ABSTRACT FROM AUTHOR]

• Pinocembrin was hybridized with fatty acids by using pancreatic porcine lipase. • Pinocembrin and its linolenoyl derivative promoted wound closure in HaCaT cells. • Wound healing activity was mediated by GPR120/β-arrestin complexation. • Wound healing was limited by pre-treatment with GPR120 antagonist AH7614. • Pinocembrin and its linolenoyl derivative share the same binding pocket of TUG-891. Wound healing represents an urgent need from the clinical point of view. Several diseases result in wound conditions which are difficult to treat, such as in the case of diabetic foot ulcer. Starting from there, the medicinal research has focused on various targets over the years, including GPCRs as new wound healing drug targets. In line with this, GPR120, known to be an attractive target in type 2 diabetes drug discovery, was studied to finalize the development of new wound healing agents. Pinocembrin (HW0) was evaluated as a suitable compound for interacting with GPR120, and was hybridized with fatty acids, which are known endogenous GPR120 ligands, to enhance the wound healing potential and GPR120 interactions. HW0 and its 7-linolenoyl derivative (HW3) were found to be innovative wound healing agents. Immunofluorescence and functional assays suggested that their activity was mediated by GPR120, and docking simulations showed that the compounds could share the same pocket occupied by the known GPR120 agonist, TUG-891. [ABSTRACT FROM AUTHOR]

[Display omitted] • Design, synthesis, and evaluation of a library of piperazine-derived small molecules. • Privileged structure-based design strategy guided the generation of the new structures. • Compounds 42 and 44 inhibited Zika and Dengue virus replication in vitro in the low micromolar range (1.4–6.7 μM). • The interactions between essential residues of NS3 active site and selected compounds were determined by docking analysis. Since 2011 Direct Acting antivirals (DAAs) drugs targeting different non-structural (NS) viral proteins (NS3, NS5A or NS5B inhibitors) have been approved for clinical use in HCV therapies. However, currently there are not licensed therapeutics to treat Flavivirus infections and the only licensed DENV vaccine, Dengvaxia, is restricted to patients with preexisting DENV immunity. Similarly to NS5 polymerase, the NS3 catalytic region is evolutionarily conserved among the Flaviviridae family sharing strong structural similarity with other proteases belonging to this family and therefore is an attractive target for the development of pan-flavivirus therapeutics. In this work we present a library of 34 piperazine-derived small molecules as potential Flaviviridae NS3 protease inhibitors. The library was developed through a privileged structures-based design and then biologically screened using a live virus phenotypic assay to determine the half-maximal inhibitor concentration (IC 50) of each compound against ZIKV and DENV. Two lead compounds, 42 and 44 , with promising broad-spectrum activity against ZIKV (IC 50 6.6 µM and 1.9 µM respectively) and DENV (IC 50 6.7 µM and 1.4 µM respectively) and a good security profile were identified. Besides, molecular docking calculations were performed to provide insights about key interactions with residues in NS3 proteases' active sites. [ABSTRACT FROM AUTHOR]