Exploring Inclusion Complex of an Antithyroid Drug (PTU) with a-Cyclodextrin for Innovative Applications by Physicochemical Approach Optimized by Molecular Docking

Herein, we aim to form the inclusion complex (IC) of an antithyroid drug 6-propyl-2-thiouracil (PTU) with a-cyclodextrin (a-CD) and to analyse its aqueous solubility, photostability, binding with Calf thymus DNA (CT-DNA), antibacterial and cytotoxic activities. The PTU-a-CD complex was synthesized by following the co-precipitation method with a molar ratio of 1:1. The formed complex was characterized by employing several spectroscopic techniques such as nuclear magnetic resonance (1H NMR), fourier transform infrared (FTIR), differential scanning calorimetry (DSC), thermo-gravimetric analysis (TGA), powder XRD and scanning electron microscopy (SEM) indicated the successful encapsulation of drug PTU into the nano cage of a-CD. The enhancement of thermal stability of PTU after complexation was shown by TGA and DSC analysis. Job's plot confirmed the 1:1 M ratio of guest (PTU) and host (a-CD) during the formation of IC and the molecular association constant as predicted between PTU and a-CD using UV-vis titration method was found to be 3297.57 +/- 0.15 M-1. The most desired orientation of the PTU molecule within the non-polar binding pocket of a-CD cavity was speculated by molecular modelling study. The PTU-a-CD complex showed better in vitro antimicrobial activity results as compared to pure drug PTU. The aqueous solubility and photostability of PTU were greatly improved owing to the formation of the PTU-a-CD complex as shown using UV-vis spectroscopy. The PTU-a-CD complex (IC50 = 2.12 mu M) also displayed noteworthy in vitro cytotoxic activity than pure PTU (IC50 = 6.44 mu M) towards human kidney cancer cell line (ACHN) whereas (IC50 = 3.63 mu M) and (IC50 = 2.09 mu M) for PTU-a-CD and drug respectively in a normal kidney cell line (HEK-293). This research also predicts the release of PTU in presence of CTDNA without any chemical alteration. Finally, these outcomes disclose that the complexation of PTU with a-CD could enhance the stability of PTU and display various applications associated with it.(c) 2023 Elsevier B.V. All rights reserved.