Hirbod, Kimia, Jalili-baleh, Leili, Nadri, Hamid, Ebrahimi, Seyed Esmaeil, Moradi, Alireza, Pakseresht, Bahar, Foroumadi, Alireza, Shafiee, Abbas, Khoobi, Mehdi. (1396). Coumarin derivatives bearing benzoheterocycle moiety: synthesis, cholinesterase inhibitory, and docking simulation study. , 20(6), 631-638. doi: 10.22038/ijbms.2017.8830
Kimia Hirbod; Leili Jalili-baleh; Hamid Nadri; Seyed Esmaeil Sadat Ebrahimi; Alireza Moradi; Bahar Pakseresht; Alireza Foroumadi; Abbas Shafiee; Mehdi Khoobi. "Coumarin derivatives bearing benzoheterocycle moiety: synthesis, cholinesterase inhibitory, and docking simulation study". , 20, 6, 1396, 631-638. doi: 10.22038/ijbms.2017.8830
Hirbod, Kimia, Jalili-baleh, Leili, Nadri, Hamid, Ebrahimi, Seyed Esmaeil, Moradi, Alireza, Pakseresht, Bahar, Foroumadi, Alireza, Shafiee, Abbas, Khoobi, Mehdi. (1396). 'Coumarin derivatives bearing benzoheterocycle moiety: synthesis, cholinesterase inhibitory, and docking simulation study', , 20(6), pp. 631-638. doi: 10.22038/ijbms.2017.8830
Hirbod, Kimia, Jalili-baleh, Leili, Nadri, Hamid, Ebrahimi, Seyed Esmaeil, Moradi, Alireza, Pakseresht, Bahar, Foroumadi, Alireza, Shafiee, Abbas, Khoobi, Mehdi. Coumarin derivatives bearing benzoheterocycle moiety: synthesis, cholinesterase inhibitory, and docking simulation study. , 1396; 20(6): 631-638. doi: 10.22038/ijbms.2017.8830

Coumarin derivatives bearing benzoheterocycle moiety: synthesis, cholinesterase inhibitory, and docking simulation study

Iranian Journal of Basic Medical Sciences
مقاله 4، دوره 20، شماره 6، 2017، صفحه 631-638    اصل مقاله (1.34 M)
نوع مقاله: Original Article
شناسه دیجیتال (DOI): 10.22038/ijbms.2017.8830
نویسندگان
Kimia Hirbod1؛ Leili Jalili-baleh2؛ Hamid Nadri3؛ Seyed Esmaeil Sadat Ebrahimi1، 2؛ Alireza Moradi3؛ Bahar Pakseresht3؛ Alireza Foroumadi2؛ Abbas Shafiee2؛ Mehdi Khoobi* 4، 5
1Department of Medical Chemistry, School of Pharmacy, International Campus, Tehran University of Medical Science, Tehran, Iran
2Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
3Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
4Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran, Iran
5Nanobiomaterials Group, Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, Tehran, Iran
چکیده
Objective(s): To investigate the efficiency of a novel series of coumarin derivatives bearing benzoheterocycle moiety as novel cholinesterase inhibitors.
Materials and Methods: Different 7-hydroxycoumarin derivatives were synthesized via Pechmann or Knoevenagel condensation and conjugated to different benzoheterocycle (8-hydroxyquinoline, 2-mercaptobenzoxazole or 2-mercaptobenzimidazole) using dibromoalkanes 3a-m. Final compounds were evaluated against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) by Ellman's method. Kinetic study of AChE inhibition and ligand-protein docking simulation were also carried out for the most potent compound 3b.
Results: Some of the compounds revealed potent and selective activity against AChE. Compound 3b containing the quinoline group showed the best activity with an IC50 value of 8.80 µM against AChE. Kinetic study of AChE inhibition revealed the mixed-type inhibition of the enzyme by compound 3b. Ligand-protein docking simulation also showed that the flexibility of the hydrophobic five carbons linker allows the quinoline ring to form π-π interaction with Trp279 in the PAS.
Conclusion: We suggest these synthesized compounds could become potential leads for AChE inhibition and prevention of AD symptoms.
کلیدواژه‌ها
acetylcholinesterase؛ Alzheimer’s disease؛ Benzoheterocycles Butyrylcholinesterase؛ Coumarin
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