ABSTRACT In this study, a series of indole‐based hydrazone derivatives ( 2a – g ) were synthesized and elucidated using various spectroscopic techniques. Their inhibitory profiles against MPO were examined by in vitro and in silico evaluations. All tested hydrazones indicated nanomolar inhibition with K i values of in the range of 48.7 to 399.7 nM against MPO. Especially compounds 2f ( K i = 48.7 nM) and 2g ( K i = 101.3 nM) showed better inhibitory effects compared to other compounds. The structure–activity relationship of all tested molecules was investigated. Density Functional Theory (DFT) calculations were performed to investigate the electronic and conformational properties of compounds 1 and 2a – g . Molecular docking studies were carried out to evaluate their binding affinities and interactions with the MPO active site. Molecular dynamics (MD) simulations were further conducted for compound 2f , which exhibited the highest inhibitory potential, to assess the stability of the MPO‐ 2f complex. Also, pharmacokinetic properties of all synthesized molecules were investigated using the SwissADME online server, which estimates ADMET parameters based on molecular descriptors. In conclusion, it was determined that in silico studies supported the experimental results.
Sünkür et al. (Sun,) studied this question.