Benzofuran and Benzo[b]thiophene‐2‐Carboxamide Derivatives as Modulators of Amyloid Beta (Aβ42) Aggregation DOI Creative Commons
Yusheng Zhao,

Kartar Singh,

Rahul C. Karuturi

et al.

ChemMedChem, Journal Year: 2024, Volume and Issue: 19(22)

Published: July 31, 2024

A group of N-phenylbenzofuran-2-carboxamide and N-phenylbenzo[b]thiophene-2-carboxamide derivatives were designed synthesized as a novel class Aβ42 aggregation modulators. In the thioflavin-T based fluorescence kinetics study, compounds 4 a, b, 5 b possessing methoxyphenol pharmacophore able to demonstrate concentration dependent inhibition with maximum 54 % observed for compound b. contrast, incorporation 4-methoxyphenyl ring in d led significant increase fibrillogenesis demonstrating their ability accelerate aggregation. Compound exhibited 2.7-fold when tested at 25 μM. These results further confirmed by electron microscopy studies which demonstrates d, modulate fibrillogenesis. Compounds provided neuroprotection mouse hippocampal neuronal HT22 cells against Aβ42-induced cytotoxicity. Molecular docking suggest that orientation bicyclic aromatic rings (either benzofuran or benzo[b]thiophene) plays major role moderating either inhibit Our findings support application these pharmacological tools study mechanisms

Language: Английский

Novel Phenoselenazines as Amyloid-β Aggregation Inhibitors DOI
Ahmed A. Hefny,

Kartar Singh,

Rahul C. Karuturi

et al.

ACS Medicinal Chemistry Letters, Journal Year: 2025, Volume and Issue: unknown

Published: March 16, 2025

A novel library of N-benzylphenoselenazine derivatives 8a-j were designed, synthesized, and evaluated as inhibitors amyloid-beta (Aβ42) aggregation. In the thioflavin T-based fluorescence aggregation kinetics assay, compounds 8i 8j exhibited excellent inhibition Aβ42 (∼91% at 25 μM), activity was comparable to that reference agents resveratrol (∼88%) methylene blue (∼95% inhibition). Both also demonstrated disaggregation properties (58% 76% respectively μM) antioxidant (80.5% 59% μM). cell culture studies, both able reduce Aβ42-mediated cytotoxicity. Computational studies suggest these interact in a narrow channel formed by N- C-termini pentamer model stabilize assembly prevent further These results demonstrate viability N-benzylphenoselenazines promising candidates target amyloid cascade Alzheimer's disease.

Language: Английский

Citations

0
Benzofuran and Benzo[b]thiophene‐2‐Carboxamide Derivatives as Modulators of Amyloid Beta (Aβ42) Aggregation DOI Creative Commons
Yusheng Zhao,

Kartar Singh,

Rahul C. Karuturi

et al.

ChemMedChem, Journal Year: 2024, Volume and Issue: 19(22)

Published: July 31, 2024

A group of N-phenylbenzofuran-2-carboxamide and N-phenylbenzo[b]thiophene-2-carboxamide derivatives were designed synthesized as a novel class Aβ42 aggregation modulators. In the thioflavin-T based fluorescence kinetics study, compounds 4 a, b, 5 b possessing methoxyphenol pharmacophore able to demonstrate concentration dependent inhibition with maximum 54 % observed for compound b. contrast, incorporation 4-methoxyphenyl ring in d led significant increase fibrillogenesis demonstrating their ability accelerate aggregation. Compound exhibited 2.7-fold when tested at 25 μM. These results further confirmed by electron microscopy studies which demonstrates d, modulate fibrillogenesis. Compounds provided neuroprotection mouse hippocampal neuronal HT22 cells against Aβ42-induced cytotoxicity. Molecular docking suggest that orientation bicyclic aromatic rings (either benzofuran or benzo[b]thiophene) plays major role moderating either inhibit Our findings support application these pharmacological tools study mechanisms

Language: Английский

Citations

2