Chemistry Proceedings

Helicenes represent a fascinating class of ortho-fused polycyclic aromatic hydrocarbons whose non-planar helical topology confers an inherent chirality on them despite a lack of stereocenters. These conjugated scaffolds play a pivotal function in asymmetric catalysis, organic optoelectronics, and supramolecular assemblies. In this context, we report the synthesis of helical carbazoles bearing an imidazole ring. The synthetic strategy involves a Sonogashira/skeletal reorganization sequence allowing the construction of the carbazole moiety, followed by a Debus–Radziszewski reaction and the Ullmann–Goldberg coupling reaction to produce helical carbazoles.

Click chemistry represents a powerful strategy for the efficient construction of biologically relevant heterocyclic scaffolds. Herein, seven topsentin and nortopsentin analogues featuring a bis(indolyl)-1,2,3-triazole framework were synthesized via Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC). Key azide and alkyne precursors were prepared through protection, reduction, nucleophilic substitution, electrophilic aromatic substitution, Sonogashira cross-coupling, and deprotection reactions. The target analogues were obtained in yields ranging from 15 to 77% and characterized by NMR spectroscopy and mass spectrometry. Their antibacterial potential was assessed against E. faecalis and E. coli. However, none of the synthesized compounds displayed antibacterial activity against either strain under the experimental conditions evaluated in this study.

Three α-aminophosphonate derivatives were synthesized via a multicomponent Kabachnik–Fields reaction involving salicylaldehyde (2-hydroxybenzaldehyde), triethyl phosphite, and three aniline derivatives. The obtained compounds were characterized by NMR (¹H, ¹³C, ³¹P) and FTIR spectroscopy. An ADMET study was then performed to evaluate their pharmacokinetic properties (absorption, distribution, metabolism, excretion, and toxicity). Among the three derivatives, compound 3b exhibited the most promising ADMET profile, with full compliance with the bioavailability radar, improved Caco-2 permeability, no CYP3A4 inhibition, and good relative solubility. Molecular docking and molecular dynamics simulations were subsequently carried out to explore their interactions with glutamate carboxypeptidase II (GCPII) and to assess the stability of the formed complexes. Compound 3a showed the most favorable binding energy (−8.28 kcal/mol) and a predicted Ki of 848.32 nM, values close to those of the co-crystallized ligand 24I (−8.34 kcal/mol; 772.92 nM). Overall, this integrated approach identifies compound 3b as the most promising candidate from a pharmacokinetic standpoint, while compound 3a displays the strongest predicted binding affinity toward GCPII, providing a solid basis for future therapeutic applications.