Exploring New Scaffolds for the Dual Inhibition of HIV-1 Rt Polymerase and Ribonuclease Associated Functions

• DOI: 10.20944/preprints202102.0525.v1
• Publication Date: 2021-02-24T08:10:54Z
• Authors: Rita Meleddu; Angela Corona; Simona Distinto; Filippo Cottiglia; Serenella Deplano; Lisa Sequeira; Daniela Secci; Alessia Onali; Erica Sanna; Francesca Esposito; Italo Cirone; Francesco Ortuso; Stefano Alcaro; Enzo Tramontano; Peter Matyus; Elias Maccioni
• Keywords: analytical_chemistry; 0301 basic medicine; HIV-RT; Anti-HIV Agents; Ribonuclease H; putative binding; Organic chemistry; Ligands; Article; HIV Reverse Transcriptase; 3. Good health; Molecular Docking Simulation; Small Molecule Libraries; Inhibitory Concentration 50; Structure-Activity Relationship; Thiazoles; 03 medical and health sciences; QD241-441; HIV-RT; ribonuclease H; dual inhibitors; docking; putative binding; docking; HIV-1; ribonuclease H; dual inhibitors

Current therapeutic protocols for the treatment of HIV infection consist of the combination of diverse anti-retroviral drugs in order to reduce the selection of resistant mutants and to allow for the use of lower doses of each single agent to reduce toxicity. However, avoiding drugs interactions and patient compliance are issues not fully accomplished so far. In this respect the identification of single agents with multitarget potential might represent the ideal solution. Accordingly, a small library of biphenylhydrazo 4-arylthiazoles derivatives has been synthesised and evaluated to investigate the ability of the new derivatives to simultaneously inhibit both associated functions of HIV reverse transcriptase. All compounds were active towards the two functions, although at different concentrations. The substitution pattern on the biphenyl moiety appears relevant to determine the activity.