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

Abstract The 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 NO 2 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 NO 2 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 Cs 2 CO 3 in DMSO. Among them, three encouraging compounds did not cause any significant cytotoxicity towards Vero cells but showed good to moderate inhibition of DENV2.