Design and Synthesis of 4-Arylazo Pyrazole Carboxamides as Dual AChE/BChE Inhibitors: Kinetic and In Silico Evaluation
Yazarlar (7)
Doç. Dr. Süleyman Akocak Türkiye
Nabıh Lolak
Türkiye
Türkiye
Doç. Dr. Hatice Esra DURAN Kafkas Üniversitesi, Türkiye
Öğr. Gör. Büşra Demir Çetinkaya Türkiye
Hamada Hashem
Stefan Bräse
Prof. Dr. Cüneyt Türkeş Erzincan Binali Yıldırım Üniversitesi, Türkiye
| Makale Türü |
Özgün Makale
(SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale)
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| Dergi Adı | PHARMACEUTICALS (Q1) | ||
| Dergi ISSN | 1424-8247 Dergi Bilgileri (2026) | ||
| Dergi Tarandığı Indeksler | SCI-Expanded | ||
| Makale Dili | Türkçe | Basım Tarihi | 01-2026 |
| Cilt / Sayı / Sayfa | 19 / 2 / – | DOI | 10.3390/ph19020239 |
| Makale Linki | https://doi.org/10.3390/ph19020239 | ||
| UAK Araştırma Alanları |
Tıbbi Biyokimya
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| Özet |
| Background/Objectives: Pyrazole carboxamides are widely used as adaptable medicinalchemistry scaffolds and have been explored as cholinesterase (ChE) inhibitor chemotypes. In this work, we prepared a new series of 4-arylazo-3, 5-diamino-N-tosyl-1H-pyrazole-1-carboxamides 5 (a–m) and evaluated their inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), supported by structure-based computational analyses. Methods: Thirteen derivatives 5 (a–m) were synthesized, fully characterized with analytical techniques (FT-IR, H NMR, and C NMR), and tested in vitro against AChE and BChE, with tacrine (THA) used as the reference inhibitor. Docking calculations were used to examine plausible binding modes. The top-ranked complexes (7XN1–5e and 4BDS–5i) were further examined by 100 ns explicit-solvent molecular dynamics (MD) simulations in Cresset Flare, followed by RMSD/RMSF analysis and contact-persistence profiling. Predicted ADME/Tox. properties were also assessed to identify potential developability issues. Results: The series showed strong ChE inhibition, and several compounds were more potent than THA. Compound 5e (4-nitro) was the most active AChE inhibitor (KI= 20.86±1.61 nM) compared with THA (KI= 164.40±20.84 nM). For BChE, the KI values ranged from 31.21 to 87.07 nM and exceeded the reference compound’s activity. MD trajectories supported stable binding in both systems (10–100 ns mean backbone RMSD: 2.21±0.17 Å for 7XN1–5e; 1.89±0.11 Å for 4BDS–5i). Most fluctuations were confined to flexible regions, while key contacts remained in place, consistent with … |
| Anahtar Kelimeler |
| pyrazole carboxamides | arylazo derivatives | acetylcholinesterase | butyrylcholinesterase | molecular docking | molecular dynamics | ADME/Tox. prediction |
BM Sürdürülebilir Kalkınma Amaçları
| Atıf Sayıları | |
| Web of Science | 10 |
| Google Scholar | 11 |