Romanian Society of Pharmaceutical Sciences
 

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SYNTHESIS, SPECTRAL CHARACTERIZATION AND MOLECULAR DOCKING STUDIES OF NEW N3-ARYL-AND N3-ALKYL-BARBITURIC ACID DERIVATIVES WITH POTENTIAL LOCAL ANAESTHETIC ACTION

TEODOR OCTAVIAN NICOLESCU 1#, GABRIELA STANCIU 2#, MAGDALENA MITITELU 3#, ADINA MAGDALENA MUSUC 4*, LUCIAN ISCRULESCU 1, DRAGOȘ PAUL MIHAI 5, FLORICA NICOLESCU

1“Carol Davila” University of Medicine and Pharmacy, Faculty of Pharmacy, Organic Chemistry Department, 3-6 Traian Vuia Street, 020956, Bucharest, Romania
2 “Ovidius” University of Constanța, Department of Chemistry and Chemical Engineering, 124 Mamaia Boulevard, 900527, Constanța, Romania
3 “Carol Davila” University of Medicine and Pharmacy, Faculty of Pharmacy, Clinical Laboratory and Food Hygiene Department, 3-6 Traian Vuia Street, 020956, Bucharest, Romania
4 “Ilie Murgulescu” Institute of Physical Chemistry, 202 Splaiul Independenței, 060021, Bucharest, Romania
5 “Carol Davila” University of Medicine and Pharmacy, Faculty of Pharmacy, Pharmacology and Clinical Pharmacy Department, 3-6 Traian Vuia Street, 020956, Bucharest, Romania
6 “Carol Davila” University of Medicine and Pharmacy, Faculty of Pharmacy, Toxicology Department, 3-6 Traian Vuia Street, 020956, Bucharest, Romania

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Azoles and their derivatives have generated increasing pharmacological interest due to their properties as well as the wide range of links between structure and biological activity. Herein, starting from Löfgren's principle regarding the synthesis of a local anaesthetic, docking studies took into account the complex architecture of voltage-gated sodium channels, the nature of the membranes, and the way of administering the local anaesthetic. Thus, the present research aims at the spectral characterization and molecular docking studies of the newly synthesized compounds containing an ester-type anaesthetic chain substituted with an azole ring, having a hydrophilic character and a pyrimidine ring, as a lipophilic group. The HPLC, FT-IR, RMN (1H- și 13C- RMN) and mass spectrometry methods were used to characterize the obtained compounds. Molecular docking studies were performed using the crystal structure of the NavAb voltage-gated sodium channel obtained from the PDB RCSB (PDB ID: 6MVX) database to predict local anaesthetic activity.