Rabbit muscle pyruvate kinase activators: Synthesis, molecular docking and theoretical studies of N-substituted sulfonamide derivatives
Küçük Resim Yok
Tarih
2024
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Elsevier
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Pyruvate kinase (PK) activators have potential therapeutic applications in diseases such as sickle cell anemia. In this study, N-Substituted sulfonamide derivatives of 1,4-dihydropyridines were synthesized and evaluated as PK activators in vitro and using molecular docking studies. The compounds were synthesized by reacting dicarbonyl compounds with ammonium acetate, 5-nitrobenzaldehyde, and alumina sulfuric acid (ASA), followed by reduction and sulfonylation. The structures of the compounds were analyzed using spectroscopic techniques. DFT calculations provided insights into the electronic properties. Molecular docking of the compounds into the active site of PK showed favorable binding interactions. ADME evaluation indicated suitable solubility, BBB permeation, and lack of CYP450 inhibition. Overall, this study demonstrates the potential of new hybrid 1,4-dihydropyridine substituted sulfonamides as PK activators for further development. According to AC50 values, the compound (DTS-F-7, 0.97 mu M) is about 100-fold higher affective than the clinically used sulfonamide compound (AC50 = 90 mu M) for PK.
Açıklama
Anahtar Kelimeler
1, 4-Dihydropyridine, Sulfonamide, Rabbit muscle pyruvate kinase, Drug Discovery, Basis-Sets, Density, 1,4-Dihydropyridines, Solubility, Absorption, Efficient, Energies
Kaynak
International Journal of Biological Macromolecules
WoS Q Değeri
N/A
Scopus Q Değeri
Q1
Cilt
274
