Crystal structure, DFT calculation, molecular docking, in vitro biological activity evaluation and in silico drug-likeness prediction of N-((1H-indol-3-yl)methyl)-4-(piperidin-1-yl)aniline

Abstract

In the thesis, a novel compound named N-((1H-indol-3-yl)methyl)-4-(piperidin-1-yl)aniline (compound C3) targeting Mycobacterium tuberculosis cyt-bd oxidase was synthesized and crystallized. Compound C3 exhibited significant activity against cyt-bd oxidase, with IC50 values of 26.63 ± 0.2 μM, and also demonstrated efficacy against MtbH37Ra, with MIC values of 16.28 ± 0.2 μM. Therefore, further research was carried out to explore the molecular structure of compound C3 and its interaction with cyt-bd oxidase. Firstly, quantum chemical calculations were carried out to predict various spectral properties of C3 including structural optimization, infrared, Raman, 1H-NMR and 13C-NMR. In addition, Hirshfeld surface analysis is used to clarify the multiple interactions of C3, while two-dimensional fingerprints can accurately quantify the intermolecular interactions. Molecular electrostatic potential (MEP) is used to determine the sites where electrostatic interactions can be formed. Furthermore, FMOs (Frontier Molecular Orbitals) were utilized to assess the chemical stability of C3. Finally, molecular docking research was carried out to study the detailed interactions between cyt-bd oxidase and compound C3. In addition, ADME (absorption, distribution, metabolism and excretion) predictions show that compound C3 has good drug-forming and pharmacokinetics characteristics.