Water-soluble non-peripheral quinoline-substituted Co(II) and Cu(II) phthalocyanines as promising multi-target enzyme inhibitors: synthesis, enzyme kinetics, and molecular docking studies
JOURNAL OF MOLECULAR STRUCTURE, cilt.1381, 2027 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 1381
- Basım Tarihi: 2027
- Doi Numarası: 10.1016/j.molstruc.2026.147760
- Dergi Adı: JOURNAL OF MOLECULAR STRUCTURE
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Chemical Abstracts Core, Chimica, Compendex, INSPEC, Academic Search Ultimate (EBSCO), Engineering Source (EBSCO)
- Recep Tayyip Erdoğan Üniversitesi Adresli: Evet
Özet
New non-peripherally quinoline-substituted cobalt(II) and copper(II) phthalocyanines and their quaternized water-soluble derivatives were synthesized, characterized, and investigated as multi-target enzyme inhibitors. The synthesized compounds were structurally confirmed by FT-IR, UV-Vis, NMR, ESI-MS, and MALDI-TOF MS analyses. The water-soluble derivatives, n-8K-C3-CuQ and n-8K-C3-CoQ, were evaluated against acetylcholinesterase (AChE), butyrylcholinesterase (BuChE), and alpha-glucosidase. Both compounds showed stronger AChE inhibition than galantamine, with IC50 values of 1.65 f 0.58 & micro;M for n-8K-C3-CuQ and 1.60 f 0.94 & micro;M for n-8K-C3-CoQ. In BuChE inhibition, n-8K-C3-CoQ exhibited the highest activity with an IC50 value of 4.71 f 1.96 & micro;M, markedly superior to galantamine. Moreover, both derivatives displayed pronounced alpha-glucosidase inhibition, with IC50 values of 1.14 f 0.85 and 1.36 f 0.49 & micro;M for n-8K-C3-CuQ and n-8K-C3-CoQ, respectively, compared with acarbose. Enzyme kinetic studies revealed enzyme-and metal-dependent inhibition mechanisms, including competitive, mixed-type, and non-competitive inhibition modes. Molecular docking analyses supported the experimental findings, with favorable binding scores toward AChE, BuChE, and alpha-glucosidase, reaching-9.0 kcal/mol. Overall, these results suggest that water-soluble quinoline-functionalized metallophthalocyanines may represent promising scaffolds for the development of multi-target cholinesterase and alpha-glucosidase inhibitors. However, further cytotoxicity, selectivity, and in vivo studies are required before their therapeutic potential can be fully established.