Synthesis, single crystal, TD-DFT, molecular dynamics simulation and DNA binding studies of carbothioamide analog

• Published in: Journal of molecular structure 2023-09, Vol.1287, p.135701, Article 135701
• Main Authors: Rana, Manish, Ahmedi, Saiema, Fatima, Aysha, Ahmad, Shaban, Nouman, Siddiqui, Nazia, Raza, Khalid, Manzoor, Nikhat, Javed, Saleem, Rahisuddin
• Format: Article
• Language: English
• Subjects: Antifungal; DNA; MD simulation; TD-DFT
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2023.135701

•The spectroscopic and X-ray single crystal studies of pyrazoline derivative.•Antifungal activity was evaluated and further studied by molecular dynamics.•FMO, UV–Vis, NBO, NHO, NLO, MEP and hirshfeld surface analysis for charge transfer studies. In this work, analog 3b (5-(4-(dimethylamino) phenyl)-3-(4-methoxyphenyl)-4,5-dihydro-1H-pyrazole-1-carbothioamide) of pyrazoline derivative was produced based on the active site (CYP51) analysis. To elucidate its molecular structure, various techniques including FT-IR, UV–visible, NMR, mass spectrometry and X-ray crystallography were utilised. The bond lengths and bond angles occur in monoclinic with P21/n space group for 3b, and z = 8 corresponds to compound 3b, and the lattice parameters show, a = 14.5480(14) Å, b = 17.0119(17) Å, c = 14.6257(14) Å, α = 90˚, β = 98.646(3)˚, γ = 90˚ per unit cell. Analog 3b also showed significant antifungal activity against candida strains, C. albicans, C. glabrata, and C. tropicalis and molecular docking performed at the active site of 14-alpha demethylase, and an estimated ADME assay was calculated. In addition, simulation of the CYP51 protein-ligand complexes at a time scale of 100 ns showed that the mean RMSD is 0.31 nm. According to the simulation and MMGBSA data, protein-ligand complexes are stable and exhibit stable interactions up to 100 ns of simulation time. The DNA binding was revealed by using UV–vis, fluorescence and cyclic voltammetry measurements. TD-DFT calculation was used to study several computational structural characteristics of molecule. We also used Hirshfeld surface analysis (HSA), FTIR, UV–Vis. and NMR spectra to compare the structural features of theoretical and experimental findings of the molecule 3b. The comprehensive in-silico and experimental study confirm the synthesised pyrazoline analog's antifungal, antioxidant, and DNA binding properties. [Display omitted]