Synthesis, characterization, crystallography insights, and larvicidal activity of 4-substituted-8-(trifluoromethyl)quinoline derivatives against Anopheles arabiensis

Synthesis, Structural Elucidation and DFT Studies of Novel Coumarin Derivative with Docking, ADMET Analysis and Antibacterial Activities

Synthesis, X-ray crystallography, DFT study of 5-chloro-2-((2-methyl-6-(trifluoromethyl)pyrimidin-4-yl)oxy)aniline, and its antifungal activity

Abstract A novel trifluoromethyl-pyrimidine derivative, 5‑chloro‑2‑((2‑methyl‑6‑(trifluoromethyl) pyrimidin‑4‑yl)oxy)aniline, was synthesized and structurally confirmed through 1H NMR, 13C NMR, FT-IR and high-resolution mass spectrometry (HRMS). The density functional theory (DFT)/B3LYP method with a 6-311 + G (2d,p) basis set was adopted to execute the title compound’s molecular structure conformational analysis. The calculated optimal structure was consistent with the crystal structure obtained from X-ray single-crystal diffraction. Furthermore, calculations of the frontier molecular orbital and molecular electrostatic potential surface maps were carried out to acquire more information. In addition, the title compound exhibited promising antifungal efficacy, highlighting its potential as a new fungicide candidate.

Synthesis, crystal structure, and preliminary acetylcholinesterase inhibitory evaluation of hydantoin and thiazolidine-2,4-dione derivatives: an experimental and computational study

Acetylcholinesterase (AChE) inhibition remains one of the most effective strategies for the symptomatic treatment of Alzheimer’s disease. Herein, a series of hydantoin and thiazolidine-2,4-dione derivatives was synthesized through condensation reactions and comprehensively characterized by NMR spectroscopy, HR-ESI-TOF-MS, and FTIR analysis. Biological evaluation against electric eel AChE identified several active compounds, with compound 3f displaying the highest inhibitory activity (93%) at 100 µg/mL. Molecular docking demonstrated that 3f adopts a binding mode like that of donepezil within the AChE active-site gorge, while molecular dynamics simulation confirmed the stability of the protein-ligand complex throughout the simulation. The crystal structure of 3f , determined by single-crystal X-ray diffraction, revealed a triclinic packing arrangement stabilized by hydrogen bonding, halogen contracts, and π-π interactions, which were further characterized by Hirshfeld surface analysis. These results establish a structural basis for the observed inhibitory activity and highlight halogenated hydantoin derivatives as potential scaffolds for the development of new AChE inhibitors.

Molecular modelling, cytotoxic activity, and carbonic anhydrase inhibition of new pyridazine-thiazole hybrid compounds

A series of novel pyridazine-thiazole compounds 6 , 7 , 9 , and 10 were synthesized by introducing various thiazole ring systems into the precursor 4-(pyridazin-3-yl)amino)benzohydrazide compound 4 . The DFT/B3LYP optimized structures of the synthesized hybrids exhibited a non-planar geometry. Frontier orbital structures of the studied derivatives were strongly influenced by structural modifications. For example, in the ester 3 and hydrazide 4 analogues, the HOMO was localized on the phenylamino-pyridazine, whereas the LUMO was mainly centered on the cyano-pyridazine moiety. While in the thiosemicarbazide hybrid 5 , the HOMO has shifted toward sulfur- and nitrogen-rich regions, indicating enhanced intramolecular charge-transfer character. The in vitro cytotoxic activity of the synthesized analogues against HepG2, HT-29, MCF-7, and WI-38 cell lines showed that analogue 10b exhibited potent activity (IC₅₀ = 22.39 ±0.16 μM) against HepG2, while analogue 8 disclosed the good activity toward HT-29, (IC₅₀ = 16.54 ±0.38 μM) and analogue 10a revealed proper efficacy (IC₅₀ = 16.44±0.31 μM) against MCF-7 higher than that of the reference doxorubicin. Besides, the carbonic anhydrase enzymes inhibitory potential against the tumor-related isoforms (CA IX and CA XII) presented hybrids 5 , 7a , 10a , and 10c as good CA IX inhibitors, comparable to the reference inhibitor acetazolamide (AZA). Meanwhile, docking with human 5FL4 protein revealed that the pyridazine-hydrazinyl analogues displayed proper bindings due to their more separate electron density and effective interactions. The pharmacokinetics SwissADME in silico studies indicated that the low molecular weight conjugates respect Lipinski’s rule of five, with optimal value of lipophilicity (iLOGP < 3.27), and exhibit blood-brain barrier permeability. While bulky derivatives showed a reduced gastrointestinal absorption (GI) absorption with increased molecular weight, topological polar surface area.

Novel 1,2,4-triazole–benzimidazole Hybrids as Potential Bioactive Scaffolds: Synthesis, Mechanistic and Molecular Docking Studies

DESIGN, CRYSTAL STRUCTURE, DFT ANDMOLECULARDOCKING STUDIES OF SCHIFF BASE DERIVEDFROMALIPHATIC DIAMINE

In the modern era, cancer has become a major health problem due to increasing environmental pollution. Thepurpose of this research is to create a new chemical that can fight against cancer cells. We introduced a Schiff basesynthesised from m-nitrobenzaldehyde and 1,3-diaminoisopropanol. The compound (HL-2SB) was elucidatedbyusing UV-Vis, IR, NMR, HRMS and SCXRD. SCXRD confirms that the HL-2SB is a monoclinic crystal with spacegroup (P21/n) system. FMO analysis of the compound gave a HOMO-LUMO gap of 4.4216 eV, indicatingtheir kinetic stability and reactivity. From DFT studies, the large electrophilicity index (6.1879 eV) showed the abilitytoresist electron removal, efficient charge transfer and stability in structure. The molecular docking studies of HL-2SBwith 8RY2 protein the strong hydrogen bonds between them. These studies reveal that the compound acts as ananticancer agent.