Functionalized imidazolium and benzimidazolium salts as paraoxonase 1 inhibitors: Synthesis,characterization and molecular docking studies |
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| Affiliation: | 1. Inönü University, Faculty of Arts and Science, Department of Chemistry, 44280 Malatya, Turkey;2. Inönü University, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, 44280 Malatya, Turkey;3. Süleyman Demirel University, Faculty of Pharmacy, Department of Biochemistry, 32260 Isparta, Turkey;4. Balıkesir University, Faculty of Arts and Science, Department of Chemistry, 10145 Balıkesir, Turkey;5. Giresun University, Faculty of Education, Department of Computer Education and Instructional Technology, 28100 Giresun, Turkey;6. Ondokuz Mayıs University, Faculty of Arts and Sciences, Department of Physics, 55139 Samsun, Turkey;1. Department of Chemistry, Faculty of Science, Atatürk University, 25240, Erzurum, Turkey;2. Department of Primary Education, Faculty of Education, Bayburt University, 69000, Bayburt, Turkey;1. School of Chemical Sciences, Universiti Sains Malaysia, 11800, USM, Penang, Malaysia;2. School of Biological Sciences, Universiti Sains Malaysia, 11800, USM, Penang, Malaysia;3. Centre for Chemical Biology, University Sains Malaysia, 11900 Penang, Malaysia;1. Centre for Nano and Material Sciences, Jain University, Jain Global Campus, Kanakapura, Ramanagaram, Bangalore, 562112, India;2. School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland;1. İnönü University, Faculty of Science, Department of Chemistry, 44280, Malatya, Turkey;2. Dokuz Eylül University, Faculty of Science, Department of Physics, 35160-Buca, İzmir, Turkey;1. Inonu University, Faculty of Science, Department of Chemistry, 44280 Malatya, Turkey;2. Ege University Faculty of Science, Department of Chemistry, 35100 Izmir, Turkey;3. Inonu University, Faculty of Medicine, Department of Microbiology, 44280 Malatya, Turkey |
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| Abstract: | Paraoxonase (PON) is a key enzyme in metabolism of living organisms and decreased activity of PON1 was acknowledged as a risk for atherosclerosis and organophosphate toxicity. The present study describes the synthesis, characterization, PON1 inhibitory properties and molecular docking studies of functionalized imidazolium and benzimidazolium salts (1a–5g). The structures of all compounds were elucidated by IR, NMR, elemental analysis and structures of compounds 2b and 2c were characterized by single-crystal X-ray diffraction. Compound 1c, a coumarin substituted imidazolium salt showed the best inhibitory effect on the activity of PON1 with good IC50 value (6.37 μM). Kinetic investigation was evaluated for this compound and results showed that this compound is competitive inhibitor of PON1 with Ki value of 2.39 μM. Molecular docking studies were also performed for most active compound 1c and one of least active compound 2c in order to determine the probable binding model into active site of PON1 and validation of the experimental results. |
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| Keywords: | Benzimidazolium Coumarin Imidazolium Inhibition Molecular docking Paraoxonase 1 |
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