Molecular Docking Studies and Biological Evaluation of Berberine-Benzothiazole Derivatives as an Anti-Influenza Agent via Blocking of Neuraminidase.

In this study, we have introduced newly synthesized substituted benzothiazole based berberine derivatives that have been analyzed for their in vitro and in silico biological properties. The activity towards various kinds of influenza virus strains by employing the cytopathic effect (CPE) and sulforhodamine B (SRB) assay. Several berberine-benzothiazole derivatives (BBDs), such as BBD1, BBD3, BBD4, BBD5, BBD7, and BBD11, demonstrated interesting anti-influenza virus activity on influenza A viruses (A/PR/8/34, A/Vic/3/75) and influenza B viral (B/Lee/40, and B/Maryland/1/59) strain, respectively. Furthermore, by testing neuraminidase activity (NA) with the neuraminidase assay kit, it was identified that BBD7 has potent neuraminidase activity. The molecular docking analysis further suggests that the BBD1-BBD14 compounds' antiviral activity may be because of interaction with residues of NA, and the same as in oseltamivir.

Berberine-piperazine conjugates as potent influenza neuraminidase blocker.

In these studies, we analyzed substituted piperazine based berberine analogs conjugated through a pentyloxy side chain for their in vitro and in silico biological effects. All the final analogs were screened for their in vitro antiviral action against a collection of different influenza virus strains using the CPE assay and SRB assay. Moreover, their cytotoxicity towards non-cancer cell lines was examined employing Madin-Darby canine kidney (MDCK) cell lines. The anti-influenza activities of berberine-piperazine derivatives (BPD) were evaluated in the range from 35.16 µg/mL to 90.25 µg/mL of the IC50s along with cytotoxicity level which was observed in the range 44.8 µg/mL to 3890.6 µg/mL of CC50s towards MDCK cells. In an effort to know the mechanism of action of BPD1-BPD23, results of Neuraminidase inhibition assay and Molecular docking studies carried out against neuraminidase as the target enzyme revealed that titled compounds are potential neuraminidase inhibitors that merge to the active site of neuraminidase, with moderate to high binding energy.