Synthesis and molecular modeling studies of naphthazarin derivatives as novel selective inhibitors of ?-glucosidase and ?-amylase
Yükleniyor...
Tarih
2023
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Elsevier B.V.
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Diabetes mellitus is known as one of the most life-threatening diseases and has attracted the attention
of medicinal chemists. The design and synthesis of novel potential candidates for the inhibition of αamylase and α-glucosidase enzymes which are responsible for the digestion of dietary carbohydrates
are an important approach for the treatment of diabetes. In this current work, a range of novel mono
and naphthazarin derivatives were successfully synthesized by the esterification reaction of naphthazarin with different benzoyl chlorides and heterocyclic acyl chlorides. The synthesized compounds were
subjected to in vitro antidiabetic activities through α-glucosidase and α-amylase inhibition properties.
Despite the limited inhibition potential against α-amylase enzymes, naphthazarin derivatives would be
promising targets for antidiabetic study due to the specificity for α-glucosidase enzyme. The compound
18 revealed a dual inhibition behavior, however all the other active compounds were detected as specific
for α-glucosidase inhibition and quite potent compared to the standard acarbose which is promising for
eliminating the side effects associated with the non-selectivity of acarbose. The compound 19 was the
best candidate for inhibition with IC50 value of 7.4 μM and resulted 150-fold better activity compared to
the standard. Free energy calculations support the experimental binding affinity of compound 19 found
as the most promising drug candidate for α-glucosidase among the synthesized compounds. The plausible binding mode and the interaction of compound 19 complexed with α-glucosidase has been revealed
by MD simulations.
Açıklama
Anahtar Kelimeler
Naphthazarin, α-amylase, α-glucosidase, Enzyme inhibition, Molecular modeling
Kaynak
Journal of Molecular Structure
WoS Q Değeri
N/A
Scopus Q Değeri
Q1
Cilt
Sayı
1278
Künye
Abadan, Ş., Sağlam, M. F., Koca, M. S., Bingül, M., Şahin, H., Zorlu, Y. ve diğerleri. (2023). Synthesis and molecular modeling studies of naphthazarin derivatives as novel selective inhibitors of α-glucosidase and α-amylase. Journal of Molecular Structure, (1278), 1-12.
