Synthesis and 2D-QSAR study of dispiropyrrolodinyl-oxindole based alkaloids as cholinesterase inhibitors |
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| Institution: | 1. College of Chemistry and Chemical Engineering, Hunan University, No.1 Lushan Road(s), Changsha 410082, China;2. College of Biology, Hunan University, No.1 Lushan Road(s), Changsha 410082, China;3. National Engineering Research Center for Agrochemicals, Hunan Research Institute of Chemical Industry, Changsha 410007, China;1. Department of Chemistry, Mirpur University of Science and Technology (MUST), 10250 Mirpur, AJK, Pakistan;2. Department of Chemistry, Khwaja Fareed University of Engineering & Information Technology, Rahim Yar Khan 64200, Pakistan;3. Instituto de Química – IQ, Universidade Federal de Goiás – UFG, Goiânia 74690-900, GO, Brazil;4. Instituto de Química – INQUI, Universidade Federal do Mato Grosso do Sul – UFMS, Campo Grande 79074-460, MS, Brazil;5. Department of Biosciences and Technology, Khwaja Fareed University of Engineering and Information Technology, Rahim Yar Khan 64200, Pakistan;6. Beijing Institute of Technology, China;7. Department of Chemistry, Faculty of Science, King Khalid University, P.O. Box 9004, Abha 61413, Saudi Arabia;8. Department of Chemistry, Government Major Muhammad Afzal Khan (Shaheed), Boys Degree College Afzalpur, Mirpur, (Affiliated with Mirpur University of Science and Technology (MUST)), 10250 Mirpur AJK, Pakistan;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11884, Egypt;2. The Regional Center for Mycology and Biotechnology, Al-Azhar University, Cairo, Egypt;3. Biomedical Sciences Program, Zewail City of Science and Technology, 12578 Cairo, Egypt |
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| Abstract: | In this work, we describe the regioselective synthesis of some new dispiroindene-2,3′-pyrrolidine-2′,3″-indoline]-1,2″(3H)-dione 4-29 attributable to the previously described methods. All the new chemical entities were assessed in-vitro as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes; while no significant inhibitory activity for the tested compounds were assigned on AChE, compounds 4, 27, 29, 28 and 15 were the most active against BChE enzyme with IC50 = 13.7 µM, 21.8 µM, 22.1 µM, 22.9 µM and 24.9 µM respectively compared to Donepezil (IC50 = 0.72 µM). Compound 4 was found to have a mixed type mode of inhibition, the bioactivity of the new chemical entities (N = 26, n = 5, R2 = 0.893, R2 cvOO = 0.831, R2 cvMO = 0.838, F = 33.32, s2 = 0.003) was elucidated via a statistically significant QSAR model utilizing CODESSA-Pro software that validated the observed results. |
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| Keywords: | Oxindole Acetylcholinesterase Butyrylcholinesterase Alzheimer’s disease Donepezil |
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