Synthesis, biological activity and docking calculations of bis-naphthoquinone derivatives from Lawsone
Yükleniyor...
Dosyalar
Tarih
2021
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Academic Press Inc.
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Some metabolic enzyme inhibitors can be used as Multi-target-Directed-Ligands (MTDL) in Medicinal chemistry therefore, synthesis and determination of alternative inhibitors are essential. In this study, novel bis-napthoquinone derivatives (5a-o) were synthesized through a multi-component cascade reaction of two molecules of 2-hydroxy-1,4-naphthoquinone with an aromatic aldehyde in basic media using triethylamine as a catalyst. This novel heterocyclic derivatives (5a-o) are applied to inhibit the carbonic anhydrase (hCA I and hCA II) isoform in low levels of nano molecules with Ki values exist between 4.62 ± 1.01 to 70.45 ± 9.03 nM for hCA I and for hCA II which is physiologically dominant Kis values are in the range of 5.61 ± 1.04 to 73.26 ± 10.25 nM. Further these novel derivatives (5a-o) efficiently inhibit AChE with Ki values in the range of 0.13 ± 0.02 to 3.16 ± 0.56 nM. The compounds are also applied for BChE with Ki values varying between 0.50 ± 0.10 to 9.23 ± 1.15 nM. For ?-glycosidase, the most efficient Ki values of 5e and 5f are 76.14 ± 9.60 and 95.27 ± 12.55 nM respectively. Finally, molecular docking calculations against enzymes (acetylcholinesterase, butyrylcholinesterase, and the human carbonic anhydrase I and II) are compared using biological activities of heterocyclic derivatives. After these calculations, an ADME/T analysis is performed to study the future medicinal use of heterocyclic derivatives from lawsone.
Açıklama
Anahtar Kelimeler
ADME/T, Cascade Synthesis, Enzyme Inhibition, Lawson, Molecular Docking
Kaynak
Bioorganic Chemistry
WoS Q Değeri
Q1
Scopus Q Değeri
Q1
Cilt
114
Sayı
Künye
Riaz, M. T., Yaqub, M., Shafiq, Z., Ashraf, A., Khalid, M., Taslimi, P., ... & Gulçin, İ. (2021). Synthesis, Biological Activity and Docking Calculations of Bis-Naphthoquinone Derivatives from Lawsone. Bioorganic Chemistry, 105069.
