Investigation of Acoramidis-based ionic liquids as potential stabilizers of transthyretin using DFT calculations, molecular docking, and ADMET studies

Transthyretin amyloidosis (ATTR) is a type of amyloidosis that characterize by abnormal deposition of the transthyretin protein in various organs. Acoramidis drug is considered a promising treatment for patients with ATTR. However, oral delivery of the insoluble Acoramidis is challenging due to its poor bioavailability and low solubility. In the present study, three Acoramidis-based ionic liquids (ILs) are reported to address this challenge. The biological activity and reactivity of these compounds evaluated using computational chemistry methods, including molecular DFT calculations, molecular docking and ADMET (Chemical absorption, distribution, metabolism, excretion, and toxicity) analysis. The solubility of the ILs is compared based on their polarity. The results showed that all ILs were more polar than the original Acoramidis. The highest dipole moment and solubility in water belonged to Acoradidis-CF 3 COOH (IL1). Also, the calculated thermochemical data indicated that IL1 was more stable than the other two ionic liquids. Molecular docking studies showed that IL1 had the highest binding affinity (− 7.5 kcalmol −1 ). In addition, it formed a greater number of critical contacts with transthyretin (TTR) residues. Also, ADMET studies suggested favorable predicted oral bioavailability for these compounds.