In silico analysis of the antisickling activity of curcuminoids and curcumin metabolites and their ADMET properties

Abstract

<title>Abstract</title> The aim of this study was to demonstrate the <italic>in silico</italic> the potential of curcuminoids and curcumin metabolites to inhibit the polymerization of HbS. Ten molecules were analyzed, including curcuminoids (curcumin, bisdemethoxycurcumin, demethoxycurcumin and cyclocurcumin) and curcumin metabolites (dihydrocurcumin, glucuronocurcumin, hexahydrocurcumin, hexahydrocurcumin, curcumin sulphate and tetrahydrocurcumin). <italic>In silico</italic> screenings were carried out by molecular docking to determine the free enthalpies of complexation and the interactions between different ligands studied and HbS. Moreover, <italic>in silico</italic> screening using the ADMET test was carried out to determine the pharmacokinetic profile of various compounds studied. The findings revealed that all the ligands can form stable complexes with HbS. The binding energies of the complexes formed between the ligands and Hb S ranged from -5.8 Kcal/moL to -8.1 Kcal/moL. These bindings between curcumin glucuronide and cyclocurcumin with HbS were stable compared with the other compounds (-8.1 Kcal/moL and -8.0 Kcal/moL). The <italic>in silico</italic> toxicity screening showed that the majority of ligands fulfilled the Lipinski and Veber rules. Thus, we believe that curcuminoids can individually or synergistically inhibit HbS polymerization and sickle cell sickling.