The Prophylactic and Multimodal Activity of Two Isatin Thiosemicarbazones against Alzheimer’s Disease In Vitro
Alzheimer’s disease (AD) is a multifactorial disorder strongly involving the formation of amyloid-β (Aβ) oligomers, which subsequently aggregate into the disease characteristic insoluble amyloid plaques, in addition to oxidative stress, inflammation and increased acetylcholinesterase activity. Moreo...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-06-01
|
| Series: | Brain Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-3425/12/6/806 |
| _version_ | 1797489353484664832 |
|---|---|
| author | Barbara Mavroidi Archontia Kaminari Dimitris Matiadis Dimitra Hadjipavlou-Litina Maria Pelecanou Athina Tzinia Marina Sagnou |
| author_facet | Barbara Mavroidi Archontia Kaminari Dimitris Matiadis Dimitra Hadjipavlou-Litina Maria Pelecanou Athina Tzinia Marina Sagnou |
| author_sort | Barbara Mavroidi |
| collection | DOAJ |
| description | Alzheimer’s disease (AD) is a multifactorial disorder strongly involving the formation of amyloid-β (Aβ) oligomers, which subsequently aggregate into the disease characteristic insoluble amyloid plaques, in addition to oxidative stress, inflammation and increased acetylcholinesterase activity. Moreover, Aβ oligomers interfere with the expression and activity of Glycogen synthase kinase-3 (GSK3) and Protein kinase B (PKB), also known as AKT. In the present study, the potential multimodal effect of two synthetic isatin thiosemicarbazones (ITSCs), which have been previously shown to prevent Aβ aggregation was evaluated. Both compounds resulted in fully reversing the Aβ-mediated toxicity in SK-NS-H cells treated with exogenous Aβ peptides at various pre-incubation time points and at 1 μM. Cell survival was not recovered when compounds were applied after Aβ cell treatment. The ITSCs were non-toxic against wild type and 5xFAD primary hippocampal cells. They reversed the inhibition of Akt and GSK-3β phosphorylation in 5xFAD cells. Finally, they exhibited good antioxidant potential and moderate lipoxygenase and acetylcholinesterase inhibition activity. Overall, these results suggest that isatin thiosemicarbazone is a suitable scaffold for the development of multimodal anti-AD agents. |
| first_indexed | 2024-03-10T00:16:17Z |
| format | Article |
| id | doaj.art-c6c6e2687b4940be9bfdba8ea43f1b24 |
| institution | Directory Open Access Journal |
| issn | 2076-3425 |
| language | English |
| last_indexed | 2024-03-10T00:16:17Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Brain Sciences |
| spelling | doaj.art-c6c6e2687b4940be9bfdba8ea43f1b242023-11-23T15:51:45ZengMDPI AGBrain Sciences2076-34252022-06-0112680610.3390/brainsci12060806The Prophylactic and Multimodal Activity of Two Isatin Thiosemicarbazones against Alzheimer’s Disease In VitroBarbara Mavroidi0Archontia Kaminari1Dimitris Matiadis2Dimitra Hadjipavlou-Litina3Maria Pelecanou4Athina Tzinia5Marina Sagnou6Institute of Biosciences & Applications, NCSR “Demokritos”, Patr. Grigoriou and Neapoleos 27, 15310 Athens, GreeceInstitute of Biosciences & Applications, NCSR “Demokritos”, Patr. Grigoriou and Neapoleos 27, 15310 Athens, GreeceInstitute of Biosciences & Applications, NCSR “Demokritos”, Patr. Grigoriou and Neapoleos 27, 15310 Athens, GreeceDepartment of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, GreeceInstitute of Biosciences & Applications, NCSR “Demokritos”, Patr. Grigoriou and Neapoleos 27, 15310 Athens, GreeceInstitute of Biosciences & Applications, NCSR “Demokritos”, Patr. Grigoriou and Neapoleos 27, 15310 Athens, GreeceInstitute of Biosciences & Applications, NCSR “Demokritos”, Patr. Grigoriou and Neapoleos 27, 15310 Athens, GreeceAlzheimer’s disease (AD) is a multifactorial disorder strongly involving the formation of amyloid-β (Aβ) oligomers, which subsequently aggregate into the disease characteristic insoluble amyloid plaques, in addition to oxidative stress, inflammation and increased acetylcholinesterase activity. Moreover, Aβ oligomers interfere with the expression and activity of Glycogen synthase kinase-3 (GSK3) and Protein kinase B (PKB), also known as AKT. In the present study, the potential multimodal effect of two synthetic isatin thiosemicarbazones (ITSCs), which have been previously shown to prevent Aβ aggregation was evaluated. Both compounds resulted in fully reversing the Aβ-mediated toxicity in SK-NS-H cells treated with exogenous Aβ peptides at various pre-incubation time points and at 1 μM. Cell survival was not recovered when compounds were applied after Aβ cell treatment. The ITSCs were non-toxic against wild type and 5xFAD primary hippocampal cells. They reversed the inhibition of Akt and GSK-3β phosphorylation in 5xFAD cells. Finally, they exhibited good antioxidant potential and moderate lipoxygenase and acetylcholinesterase inhibition activity. Overall, these results suggest that isatin thiosemicarbazone is a suitable scaffold for the development of multimodal anti-AD agents.https://www.mdpi.com/2076-3425/12/6/806isatin thiosemicarbazonesAktGSK-3βAβ cytotoxicityacetylcholinesterase inhibitors |
| spellingShingle | Barbara Mavroidi Archontia Kaminari Dimitris Matiadis Dimitra Hadjipavlou-Litina Maria Pelecanou Athina Tzinia Marina Sagnou The Prophylactic and Multimodal Activity of Two Isatin Thiosemicarbazones against Alzheimer’s Disease In Vitro Brain Sciences isatin thiosemicarbazones Akt GSK-3β Aβ cytotoxicity acetylcholinesterase inhibitors |
| title | The Prophylactic and Multimodal Activity of Two Isatin Thiosemicarbazones against Alzheimer’s Disease In Vitro |
| title_full | The Prophylactic and Multimodal Activity of Two Isatin Thiosemicarbazones against Alzheimer’s Disease In Vitro |
| title_fullStr | The Prophylactic and Multimodal Activity of Two Isatin Thiosemicarbazones against Alzheimer’s Disease In Vitro |
| title_full_unstemmed | The Prophylactic and Multimodal Activity of Two Isatin Thiosemicarbazones against Alzheimer’s Disease In Vitro |
| title_short | The Prophylactic and Multimodal Activity of Two Isatin Thiosemicarbazones against Alzheimer’s Disease In Vitro |
| title_sort | prophylactic and multimodal activity of two isatin thiosemicarbazones against alzheimer s disease in vitro |
| topic | isatin thiosemicarbazones Akt GSK-3β Aβ cytotoxicity acetylcholinesterase inhibitors |
| url | https://www.mdpi.com/2076-3425/12/6/806 |
| work_keys_str_mv | AT barbaramavroidi theprophylacticandmultimodalactivityoftwoisatinthiosemicarbazonesagainstalzheimersdiseaseinvitro AT archontiakaminari theprophylacticandmultimodalactivityoftwoisatinthiosemicarbazonesagainstalzheimersdiseaseinvitro AT dimitrismatiadis theprophylacticandmultimodalactivityoftwoisatinthiosemicarbazonesagainstalzheimersdiseaseinvitro AT dimitrahadjipavloulitina theprophylacticandmultimodalactivityoftwoisatinthiosemicarbazonesagainstalzheimersdiseaseinvitro AT mariapelecanou theprophylacticandmultimodalactivityoftwoisatinthiosemicarbazonesagainstalzheimersdiseaseinvitro AT athinatzinia theprophylacticandmultimodalactivityoftwoisatinthiosemicarbazonesagainstalzheimersdiseaseinvitro AT marinasagnou theprophylacticandmultimodalactivityoftwoisatinthiosemicarbazonesagainstalzheimersdiseaseinvitro AT barbaramavroidi prophylacticandmultimodalactivityoftwoisatinthiosemicarbazonesagainstalzheimersdiseaseinvitro AT archontiakaminari prophylacticandmultimodalactivityoftwoisatinthiosemicarbazonesagainstalzheimersdiseaseinvitro AT dimitrismatiadis prophylacticandmultimodalactivityoftwoisatinthiosemicarbazonesagainstalzheimersdiseaseinvitro AT dimitrahadjipavloulitina prophylacticandmultimodalactivityoftwoisatinthiosemicarbazonesagainstalzheimersdiseaseinvitro AT mariapelecanou prophylacticandmultimodalactivityoftwoisatinthiosemicarbazonesagainstalzheimersdiseaseinvitro AT athinatzinia prophylacticandmultimodalactivityoftwoisatinthiosemicarbazonesagainstalzheimersdiseaseinvitro AT marinasagnou prophylacticandmultimodalactivityoftwoisatinthiosemicarbazonesagainstalzheimersdiseaseinvitro |