Design, Synthesis, and Preclinical Bio Evaluation of Chemical Conjugates Derived from Phytophenols and Nitrobenzoate as First Plausible Inhibitors of MPO Useful in CVD Treatment
Biointerface Research in Applied Chemistry · 2020
Phytophenols are important phytonutrients and useful building blocks for medicinal chemistry research. Designed conjugates derived from phytophenols and nitrobenzoate were evaluated for MPO inhibition using in-silico docking and ADMET studies. Hit to lead compounds were prepared and confirmed by NMR, mass, and single-crystal XRD analysis. Based on the in-silico study, an in-vitro MPO inhibition assay was performed and identified two best compounds 1 and 2 (MPO-IC50 value is 12.88 and 14.97 µM respectively) lead molecules. An ex-vivo anti-inflammatory study was performed with human erythrocyte hemolysis using coagulated blood cells with increasing concentration (20 to 100 µM) of the lead molecules. The activity range was found to be ~85% and ~75% for compounds 1 and 2, respectively. DPPH and ABTS radical scavenging assays of the lead molecules were compared with ascorbic acid (positive control). MTT-cell line study shows that lead compounds were non-toxic even at higher concentrations. The outcome of this study demonstrated that conjugates 1 and 2 be considered potent inhibitors of MPO and useful cardiovascular therapeutic agents.