Nanoarchitectonics and Molecular Docking of 4-(Dimethylamino)Pyridin-1-Ium 2-3 Methyl-4-Oxo-Pyri-Do[1,2-<i>a</i>]Pyrimidine-3-Carboxylate
Sanae Lahmidi,
El Hassane Anouar,
Walid Ettahiri,
Mohamed El Hafi,
Fatima Lazrak,
Mohammed M. Alanazi,
Ashwag S. Alanazi,
Mohamed Hefnawy,
El Mokhtar Essassi,
Joel T. Mague
Affiliations
Sanae Lahmidi
Laboratory of Heterocyclic Organic Chemistry, Department of Chemistry, Faculty of Sciences, Mohammed V University in Rabat, Rabat 10106, Morocco
El Hassane Anouar
Department of Chemistry, College of Science and Humanities in Al-Kharj, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia
Walid Ettahiri
Laboratory of Electrochemistry, Modelisation and Environment Engineering, Department of Chemistry, Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University in Fez, Fez 30000, Morocco
Mohamed El Hafi
Laboratory of Heterocyclic Organic Chemistry, Department of Chemistry, Faculty of Sciences, Mohammed V University in Rabat, Rabat 10106, Morocco
Fatima Lazrak
Laboratory of Medicinal Chemistry, Drug Sciences Research Center, Faculty of Medicine and Pharmacy, Mohammed V University in Rabat, Rabat 10106, Morocco
Mohammed M. Alanazi
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
Ashwag S. Alanazi
Department of Pharmaceutical Sciences, College of Pharmacy, Princess Nourah Bint Abdulrahman University, Riyadh 11671, Saudi Arabia
Mohamed Hefnawy
Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, Riyadh 11451, Saudi Arabia
El Mokhtar Essassi
Laboratory of Heterocyclic Organic Chemistry, Department of Chemistry, Faculty of Sciences, Mohammed V University in Rabat, Rabat 10106, Morocco
Joel T. Mague
Department of Chemistry, Tulane University, New Orleans, LA 70118, USA
A retro-Claisen reaction of 1-(4-oxo-4H-pyrido [1,2-a]pyrimidin-3-yl)butane-1,3-dione, 3, in the presence of potassium hydroxide and 4-dimethylamino-pyridine has been carried out, leading to 4-(dimethylamino)pyridin-1-ium 2-methyl-4-oxo-pyrido [1,2-a]pyrimidine-3-carboxylate 5. A plausible mechanism explaining the formation of the title compound has been proposed. A single-crystal X-ray diffraction analysis confirms the crystal structure of the isolated organic salt (5). In the crystal, the title compound adopts a layered structure where there are stacks of cations and anions formed by slipped π-stacking interactions. These stacks are linked by regions consisting of water molecules that are hydrogen-bonded together. DFT and Hirshfeld surface analysis supported the experimental results of the molecular geometry and the intercontacts between different units in the crystal. The druglikeness, ADMET properties, and predicted targets were investigated, and the observed results suggest that 5 may act as a carbonic anhydrase I inhibitor. The assumption is confirmed by docking 5 into the active binding site of carbonic anhydrase, which shows it to have good binding affinities and to form stable complexes with the active residues of carbonic anhydrase I.
