An in Vitro and in Silico Α-Amylase/α-glucosidase/protein Tyrosine Phosphatase 1 Beta & Radical Scavenging Profiling of the 3,5,7-Tricarbo Substituted 1H-Indazoles

A series of 3,5,7-tricarbo substituted indazoles was synthesized and evaluated for inhibitory effect in vitro against α-amylase, α-glucosidase and protein tyrosine phosphatase 1 beta (PTP1B) activities, as well as for antioxidant properties through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) radical scavenging assays. A cell-based antioxidant activity assay involving lipopolysaccharide (LPS) induced reactive oxygen species production has also been conducted. These compounds were found to exhibit increased inhibitory effect against α-amylase and PTP1B activities, and reduced activity towards α-glucosidase activity was observed. The most active compounds against these biochemical targets, namely, 2b, 2d, 2e, 2i, 2k, 2l and 2o exhibited reduced cytotoxicity against the normal green monkey kidney (Vero) cells and the adenocarcinomic human epithelial (A549) cell line. Kinetics (in vitro) and molecular docking (in silico) studies have been undertaken on the most active derivative from each series against α-amylase and PTP1B to rationalize the mechanism of drug-receptor interaction. The key aspects of the pharmacokinetics of these compounds, namely, absorption, distribution, metabolism, and excretion have also been simulated at a theoretical level.