A thiazepino[4,5-a]benzimidazole derivative hampers the RNA replication of Eurasian serotypes of foot-and-mouth disease virus.

The stamping-out policy for the control of foot-and-mouth disease virus (FMDV) in countries that are free from FMD without vaccination has a dramatic socio-economic impact, huge animal welfare issues and may result in the loss of farm animal genetic resources. As an alternative to pre-emptive culling or emergency vaccination we further explore the possibility to use antiviral drugs in the event of an FMD outbreak. In the present study, we tested the in vitro cytotoxicity and anti-FMDV activity of 1,2,4,5-tetrahydro-[1,4]thiazepino[4,5-a]benzimidazole.

Diketoacid chelating ligands as dual inhibitors of HIV-1 integration process.

HIV-1 Integrase (IN) represents a very attractive pharmacological target for the development of new and more efficient drugs. Recently, an allosteric inhibitory approach also emerged, that targets the interaction between IN and cellular cofactors, such as LEDGF/p75. Small molecules based on the diketoacid pharmachophore were studied for their ability to inhibit at the same time integration and IN-LEDGF/p75 interaction (dual inhibitors): in this study, we evaluated three indole diketoacid derivatives and their magnesium(II) complexes for their ability to act as dual inhibitors.

A new potential approach to block HIV-1 replication via protein-protein interaction and strand-transfer inhibition.

Therapeutic treatment of AIDS is recently characterized by a crescent effort towards the identification of multiple ligands able to target different steps of HIV-1 life cycle. Taking into consideration our previously obtained SAR information and combining some important chemical structural features we report herein the synthesis of novel benzyl-indole derivatives as anti-HIV agents. Through this work we identified new dual target small molecules able to inhibit both IN-LEDGF/p75 interaction and the IN strand-transfer step considered as two crucial phases of viral life cycle.

Design and synthesis of N₁-aryl-benzimidazoles 2-substituted as novel HIV-1 non-nucleoside reverse transcriptase inhibitors.

A series of novel N1-aryl-2-arylthioacetamido-benzimidazoles were synthesized and evaluated as inhibitors of human immunodeficiency virus type-1 (HIV-1). Some of them proved to be effective in inhibiting HIV-1 replication at submicromolar and nanomolar concentration acting as HIV-1 non-nucleoside RT inhibitors (NNRTIs), with low cytotoxicity. The preliminary structure-activity relationship (SAR) of these new derivatives was discussed and rationalized by docking studies.

Synthesis, modelling and biological characterization of 3-substituted-1H-indoles as ligands of GluN2B-containing N-methyl-d-aspartate receptors.

A three-step synthetic pathway has been employed to synthesize a small library of 2-(4-arylpiperidin-1-yl)-1-(1H-indol-3-yl)ethanone and 2-(4-arylpiperidin-1-yl)-1-(1H-indol-3-yl)ethane-1,2-dione derivatives that have been screened in [(3)H]ifenprodil competition binding assay. Some compounds exhibited significant binding affinity at nanomolar concentration, the most active being ligand 35 (IC50=5.5nM).