A B S T R A C T
Liver pyruvate kinase (PKL) is a key player in controlling metabolic pathways and ATP production within theliver’s glycolysis pathway. Since PKL modulators have been identified as a promising target for treating hepatocellularcarcinoma (HCC) and non-alcoholic fatty liver disease (NAFLD), our research is centered on thedevelopment and synthesis of derivatives of N-(3-cyano-4,5,6,7-tetrahydrobenzo[b]thiophen-2-yl) naphthalene-1-sulfonamide with the aim of modulating PLK. To improve PKL specificity, we used structural analysis andmodeling as a guide. Notably, compound PKL-05 became the series’ only active ingredient. DFT, Hirshfeldsurface analysis, and molecular docking were used in our study to thoroughly examine the connection betweencompound structures and their computational functions. The global hardness and softness energy values, as wellas the HOMO-LUMO energy gap value, were computed in order to forecast the chemical reactivity of this newlysynthesized molecule. These energy values indicate that this molecule tends to be chemically stable and has littlechemical reactivity. The results demonstrated a strong agreement between theoretical forecasts and experimentalfindings. In particular, PKL-05 exhibits encouraging traits that establish it as a useful starting point for additionalresearch in the search for innovative PKL modulators to tackle the treatment issues associated with NAFLD andHCC.
