Novel inhibitors with sulfamethazine backbone: synthesis and biological study of multi-target cholinesterases and α-glucosidase inhibitors

Türkeş, Cüneyt; Akocak, Süleyman; Işık, Mesut; Lolak, Nebih; Taslımı, Parham; Durgun, Mustafa; Gülçin, İlhami; BUDAK, YAKUP; Beydemir, Şükrü

doi:10.1080/07391102.2021.1916599

Novel inhibitors with sulfamethazine backbone: synthesis and biological study of multi-target cholinesterases and α-glucosidase inhibitors

Yazarlar (9)

Cüneyt Türkeş
Erzincan Binali Yıldırım Üniversitesi, Türkiye

Süleyman Akocak
Adıyaman Üniversitesi, Türkiye

Mesut Işık
Bilecik Şeyh Edebali Üniversitesi, Türkiye

Nebih Lolak
Adıyaman Üniversitesi, Türkiye

Parham Taslımı
Bartın Üniversitesi, Türkiye

Mustafa Durgun
Harran Üniversitesi, Türkiye

İlhami Gülçin
Atatürk Üniversitesi, Türkiye

Prof. Dr. Yakup BUDAK Tokat Gaziosmanpaşa Üniversitesi, Türkiye

Şükrü Beydemir
Anadolu Üniversitesi, Türkiye

Makale Türü	Özgün Makale
Makale Alt Türü	SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale
Dergi Adı	Journal of Biomolecular Structure and Dynamics
Dergi ISSN	0739-1102 Wos Dergi Scopus Dergi
Dergi Tarandığı Indeksler	SCI-Expanded
Dergi Grubu	Q1
Makale Dili	İngilizce
Basım Tarihi	10-2022
Cilt No	40
Sayı	19
Sayfalar	8752 / 8764
DOI Numarası	10.1080/07391102.2021.1916599
Makale Linki	http://dx.doi.org/10.1080/07391102.2021.1916599

Özet

The underlying cause of many metabolic diseases is abnormal changes in enzyme activity in metabolism. Inhibition of metabolic enzymes such as cholinesterases (ChEs; acetylcholinesterase, AChE and butyrylcholinesterase, BChE) and α-glucosidase (α-GLY) is one of the accepted approaches in the treatment of Alzheimer’s disease (AD) and diabetes mellitus (DM). Here we reported an investigation of a new series of novel ureido-substituted derivatives with sulfamethazine backbone (2a-f) for the inhibition of AChE, BChE, and α-GLY. All the derivatives demonstrated activity in nanomolar levels as AChE, BChE, and α-GLY inhibitors with K I values in the range of 56.07–204.95 nM, 38.05–147.04 nM, and 12.80–79.22 nM, respectively. Among the many strong N-(4,6-dimethylpyrimidin-2-yl)-4-(3-substitutedphenylureido) benzenesulfonamide derivatives (2a-f) detected against ChEs, compound 2c, the 4-fluorophenylureido derivative, demonstrated the most potent inhibition profile towards AChE and BChE. A comprehensive ligand/receptor interaction prediction was performed in silico for the three metabolic enzymes providing molecular docking investigation using Glide XP, MM-GBSA, and ADME-Tox modules. The present research reinforces the rationale behind utilizing inhibitors with sulfamethazine backbone as innovative anticholinergic and antidiabetic agents with a new mechanism of action, submitting propositions for the rational design and synthesis of novel strong inhibitors targeting ChEs and α-GLY. Communicated by Ramaswamy H. Sarma.

Anahtar Kelimeler

Acetylcholinesterase | butyrylcholinesterase | in silico study | sulfamethazine | α-glucosidase

BM Sürdürülebilir Kalkınma Amaçları

Atıf Sayıları
SCOPUS	94

Novel inhibitors with sulfamethazine backbone: synthesis and biological study of multi-target cholinesterases and α-glucosidase inhibitors

Dergi Adı	JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS
Yayıncı	Taylor and Francis Ltd.
Açık Erişim	Hayır
ISSN	0739-1102
E-ISSN	1538-0254
CiteScore	8,3
SJR	0,552
SNIP	0,792

Novel inhibitors with sulfamethazine backbone: synthesis and biological study of multi-target cholinesterases and α-glucosidase inhibitors

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