In Silico Evaluation of 1‐Aminoisoquinoline Derivatives against Dengue Virus: Greener Access via a Sonochemical Method

Abstract

AbstractThe reported antiviral properties of isoquinolines including that of berberine against dengue virus prompted us exploring a series of 1‐aminoisoquinoline derivatives against RdRp and MTase domain of NS5 protein of dengue virus (DENV) in silico. While MTase is known to assists in viral RNA capping, the RdRp plays a key role in the virus replication. The docking of 1‐aminoisoquinolines into the DENV NS5 protein RdRp domain (PDB: 5I3Q) in silico revealed good interactions of one molecule involving the H‐bond interactions through its NO2 group with GLN802, LEU511 and HIS512 residues. Notably, the docking of these compounds into the DENV NS5 protein DENV3 MTase (PDB: 5EHG) in silico also indicated same molecule as the most encouraging potential entity as the molecule participated in three H‐bond interactions through its NO2 group with GLY86, TRP87, SER56 residues. The synthesis of 1‐aminoisoquinolines was undertaken under sonochemical conditions via the reaction of 1‐chloroisoquinoline with appropriate amines in the presence of Cs2CO3 in DMSO. Among them, three encouraging compounds did not cause any significant cytotoxicity towards Vero cells but showed good to moderate inhibition of DENV2.