Novel asymmetric biscarbothioamides as Alzheimers disease associated cholinesterase inhibitors: synthesis, biological activity, and molecular docking studies

MUĞLU, Halit; Yakan, Hasan; Erdoğan, Musa; Topal, Fevzi; Topal, Meryem; Türkeş, Cüneyt; Beydemir, Şükrü

doi:10.1039/d4nj01462f

Novel asymmetric biscarbothioamides as Alzheimers disease associated cholinesterase inhibitors: synthesis, biological activity, and molecular docking studies

Yazarlar (7)

Prof. Dr. Halit MUĞLU Kastamonu Üniversitesi, Türkiye

Doç. Dr. Hasan Yakan Ondokuz Mayıs Üniversitesi, Türkiye

Musa Erdoğan Kafkas Üniversitesi, Türkiye

Fevzi Topal Gümüşhane Üniversitesi, Türkiye

Meryem Topal Gümüşhane Üniversitesi, Türkiye

Prof. Dr. Cüneyt Türkeş Erzincan Binali Yıldırım Üniversitesi, Türkiye

Prof. Dr. Şükrü Beydemir Anadolu Üniversitesi, Türkiye

Makale Türü	Özgün Makale (SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale)
Dergi Adı	New Journal of Chemistry (Q3)
Dergi ISSN	1144-0546 Wos Dergi Scopus Dergi
Dergi Tarandığı Indeksler	SCI-Expanded
Makale Dili	İngilizce	Basım Tarihi	06-2024
Cilt / Sayı / Sayfa	48 / 24 / 10979–10989	DOI	10.1039/d4nj01462f
Makale Linki	http:// 10.1039/d4nj01462f

Özet

Exploring novel frameworks for treating Alzheimer's disease is an ambitious objective. In this particular context, a range of asymmetric biscarbothioamide derivatives (3a-l) with varying substitutions have been meticulously designed and effectively synthesized. The newly synthesized compounds have all been definitively characterized using established spectroscopic techniques such as ¹H-NMR, ¹³C-NMR, FT-IR, and elemental analysis. In vitro, all the derivatives (3a-l) were evaluated to assess their inhibitory potential against cholinesterase enzymes (acetylcholinesterase, AChE, and butyrylcholinesterase, BChE). The outcomes demonstrated that these derivatives were potent and exhibited selectivity in inhibiting AChE, except for compounds 3b and 3e, which specifically inhibited BChE, showcasing varying degrees of KI values. Significantly, compounds 3j (KIs of 11.91 ± 2.25 nM for AChE and 77.76 ± 8.02 nM for BChE) and 3h (KIs of 14.73 ± 2.30 nM for AChE and 59.54 ± 6.20 nM for BChE) emerged as the most potent dual inhibitors of AChE and BChE within the series, respectively, with KI constants even lower than those of the standard drug tacrine (KIs of 68.70 ± 5.39 nM for AChE and 111.60 ± 10.52 nM for BChE). Furthermore, their potential scavenging activity against DPPH and ABTS radicals was evaluated. To further validate the experimental findings, molecular docking studies were performed in silico to ascertain the binding modes of these compounds with the active pockets of AChE and BChE enzymes.

Anahtar Kelimeler

BM Sürdürülebilir Kalkınma Amaçları

Atıf Sayıları
Scopus	22

Novel asymmetric biscarbothioamides as Alzheimers disease associated cholinesterase inhibitors: synthesis, biological activity, and molecular docking studies

Dergi Adı	NEW JOURNAL OF CHEMISTRY
Yayıncı	Royal Society of Chemistry
Açık Erişim	Hayır
ISSN	1144-0546
E-ISSN	1369-9261
CiteScore	5,0
SJR	0,493
SNIP	0,521

Novel asymmetric biscarbothioamides as Alzheimers disease associated cholinesterase inhibitors: synthesis, biological activity, and molecular docking studies

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