Screening of Some Sulfonamide and Sulfonylurea Derivatives as Anti-Alzheimer’s Agents Targeting BACE1 and PPARγ
In the last few decades, Alzheimer’s disease (AD) has emerged as a serious global problem, and it has been considered as the most common type of dementia. PPARγ and beta-secretase 1 (BACE1) are considered as potential targets for Alzheimer’s disease management. In the same time, sulfonylureas and su...
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Hindawi Limited
2020-01-01
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| Series: | Journal of Chemistry |
| Online Access: | http://dx.doi.org/10.1155/2020/1631243 |
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doaj-abd817b62f874b1e8809af4e675480c02020-11-25T03:55:49ZengHindawi LimitedJournal of Chemistry2090-90632090-90712020-01-01202010.1155/2020/16312431631243Screening of Some Sulfonamide and Sulfonylurea Derivatives as Anti-Alzheimer’s Agents Targeting BACE1 and PPARγNing Li0Yan Wang1Wensheng Li2Haiyan Li3Liu Yang4Jun Wang5Hazem A. Mahdy6Ahmed B. M. Mehany7Dareen A. Jaiash8Eman Y. Santali9Ibrahim H. Eissa10Department of Neurology, The Third Hospital of Jinan, Shandong, Jinan 250132, ChinaDepartment of Neurology, People’s Hospital of Danyang, Jiangsu, Danyang 212300, ChinaDepartment of Neurology, No. 1 Hospital, Handan 056002, Hebei, ChinaDepartment of Neurology, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, ChinaDepartment of Neurology, Emergency Medical Center of Chongqing, Chongqing 400014, ChinaDepartment of Neurology, The First People’s Hospital of Taizhou, Zhejiang, Taizhou 318020, ChinaPharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, EgyptZoology Department, Faculty of Science, Al-Azhar University, Cairo 11884, EgyptPharmaceutical Chemistry Department, College of Pharmacy, Taif University, Taif 21974, Saudi ArabiaPharmaceutical Chemistry Department, College of Pharmacy, Taif University, Taif 21974, Saudi ArabiaPharmaceutical Medicinal Chemistry & Drug Design Department, Faculty of Pharmacy (Boys), Al-Azhar University, Cairo 11884, EgyptIn the last few decades, Alzheimer’s disease (AD) has emerged as a serious global problem, and it has been considered as the most common type of dementia. PPARγ and beta-secretase 1 (BACE1) are considered as potential targets for Alzheimer’s disease management. In the same time, sulfonylureas and sulfonamides have been confirmed to have PPARγ agonistic activity. Aiming to obtain new anti-AD agents, thirty-five compounds of sulfonamide and sulfonylurea derivatives having the same essential pharmacophoric features of the reported PPARγ agonists have been subjected to virtual screening. Docking studies revealed that five compounds (1, 2, 3, 4, and 5) have promising affinities to PPARγ. They were also docked into the binding site of BACE1. In addition, ADMET and physicochemical properties of these compounds were considered. Additionally, these compounds were further evaluated against BACE1 and PPARγ. Compound 2 showed IC50 value of 1.64 μM against BACE1 and EC50 value of 0.289 μM against PPARγ.http://dx.doi.org/10.1155/2020/1631243 |
| collection |
DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Ning Li Yan Wang Wensheng Li Haiyan Li Liu Yang Jun Wang Hazem A. Mahdy Ahmed B. M. Mehany Dareen A. Jaiash Eman Y. Santali Ibrahim H. Eissa |
| spellingShingle |
Ning Li Yan Wang Wensheng Li Haiyan Li Liu Yang Jun Wang Hazem A. Mahdy Ahmed B. M. Mehany Dareen A. Jaiash Eman Y. Santali Ibrahim H. Eissa Screening of Some Sulfonamide and Sulfonylurea Derivatives as Anti-Alzheimer’s Agents Targeting BACE1 and PPARγ Journal of Chemistry |
| author_facet |
Ning Li Yan Wang Wensheng Li Haiyan Li Liu Yang Jun Wang Hazem A. Mahdy Ahmed B. M. Mehany Dareen A. Jaiash Eman Y. Santali Ibrahim H. Eissa |
| author_sort |
Ning Li |
| title |
Screening of Some Sulfonamide and Sulfonylurea Derivatives as Anti-Alzheimer’s Agents Targeting BACE1 and PPARγ |
| title_short |
Screening of Some Sulfonamide and Sulfonylurea Derivatives as Anti-Alzheimer’s Agents Targeting BACE1 and PPARγ |
| title_full |
Screening of Some Sulfonamide and Sulfonylurea Derivatives as Anti-Alzheimer’s Agents Targeting BACE1 and PPARγ |
| title_fullStr |
Screening of Some Sulfonamide and Sulfonylurea Derivatives as Anti-Alzheimer’s Agents Targeting BACE1 and PPARγ |
| title_full_unstemmed |
Screening of Some Sulfonamide and Sulfonylurea Derivatives as Anti-Alzheimer’s Agents Targeting BACE1 and PPARγ |
| title_sort |
screening of some sulfonamide and sulfonylurea derivatives as anti-alzheimer’s agents targeting bace1 and pparγ |
| publisher |
Hindawi Limited |
| series |
Journal of Chemistry |
| issn |
2090-9063 2090-9071 |
| publishDate |
2020-01-01 |
| description |
In the last few decades, Alzheimer’s disease (AD) has emerged as a serious global problem, and it has been considered as the most common type of dementia. PPARγ and beta-secretase 1 (BACE1) are considered as potential targets for Alzheimer’s disease management. In the same time, sulfonylureas and sulfonamides have been confirmed to have PPARγ agonistic activity. Aiming to obtain new anti-AD agents, thirty-five compounds of sulfonamide and sulfonylurea derivatives having the same essential pharmacophoric features of the reported PPARγ agonists have been subjected to virtual screening. Docking studies revealed that five compounds (1, 2, 3, 4, and 5) have promising affinities to PPARγ. They were also docked into the binding site of BACE1. In addition, ADMET and physicochemical properties of these compounds were considered. Additionally, these compounds were further evaluated against BACE1 and PPARγ. Compound 2 showed IC50 value of 1.64 μM against BACE1 and EC50 value of 0.289 μM against PPARγ. |
| url |
http://dx.doi.org/10.1155/2020/1631243 |
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