Synthesis and structure-activity relationship (SAR) studies of 1,2,3-triazole, amide, and ester-based benzothiazole derivatives as potential molecular probes for tau protein

Hendris Wongso; Maiko Ono; Tomoteru Yamasaki; Katsushi Kumata; Makoto Higuchi; Ming Rong Zhang; Michael J. Fulham; Andrew Katsifis; Paul A. Keller

doi:10.1039/d2md00358a

Synthesis and structure-activity relationship (SAR) studies of 1,2,3-triazole, amide, and ester-based benzothiazole derivatives as potential molecular probes for tau protein

Hendris Wongso, Maiko Ono, Tomoteru Yamasaki, Katsushi Kumata, Makoto Higuchi, Ming Rong Zhang, Michael J. Fulham, Andrew Katsifis, Paul A. Keller

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

The pyridinyl-butadienyl-benzothiazole (PBB3 15) scaffold was used to develop tau ligands with improved in vitro and in vivo properties for imaging applications to provide insights into the etiology and characteristics of Alzheimer's disease. The photoisomerisable trans-butadiene bridge of PBB3 was replaced with 1,2,3-triazole, amide, and ester moieties and in vitro fluorescence staining studies revealed that triazole derivatives showed good visualisation of Aβ plaques, but failed to detect the neurofibrillary tangles (NFTs) in human brain sections. However, NFTs could be observed using the amide 110 and ester 129. Furthermore, the ligands showed low to high affinities (K_i = >1.5 mM-0.46 nM) at the shared binding site(s) with PBB3.

Original language	English
Pages (from-to)	858-868
Number of pages	11
Journal	RSC Medicinal Chemistry
Volume	14
Issue number	5
DOIs	https://doi.org/10.1039/d2md00358a
Publication status	Published - 27-01-2023
Externally published	Yes

All Science Journal Classification (ASJC) codes

Biochemistry
Molecular Medicine
Pharmacology
Pharmaceutical Science
Drug Discovery
Organic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Wongso, H., Ono, M., Yamasaki, T., Kumata, K., Higuchi, M., Zhang, M. R., Fulham, M. J., Katsifis, A., & Keller, P. A. (2023). Synthesis and structure-activity relationship (SAR) studies of 1,2,3-triazole, amide, and ester-based benzothiazole derivatives as potential molecular probes for tau protein. RSC Medicinal Chemistry, 14(5), 858-868. https://doi.org/10.1039/d2md00358a

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title = "Synthesis and structure-activity relationship (SAR) studies of 1,2,3-triazole, amide, and ester-based benzothiazole derivatives as potential molecular probes for tau protein",

abstract = "The pyridinyl-butadienyl-benzothiazole (PBB3 15) scaffold was used to develop tau ligands with improved in vitro and in vivo properties for imaging applications to provide insights into the etiology and characteristics of Alzheimer's disease. The photoisomerisable trans-butadiene bridge of PBB3 was replaced with 1,2,3-triazole, amide, and ester moieties and in vitro fluorescence staining studies revealed that triazole derivatives showed good visualisation of Aβ plaques, but failed to detect the neurofibrillary tangles (NFTs) in human brain sections. However, NFTs could be observed using the amide 110 and ester 129. Furthermore, the ligands showed low to high affinities (Ki = >1.5 mM-0.46 nM) at the shared binding site(s) with PBB3.",

author = "Hendris Wongso and Maiko Ono and Tomoteru Yamasaki and Katsushi Kumata and Makoto Higuchi and Zhang, {Ming Rong} and Fulham, {Michael J.} and Andrew Katsifis and Keller, {Paul A.}",

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Wongso, H, Ono, M, Yamasaki, T, Kumata, K, Higuchi, M, Zhang, MR, Fulham, MJ, Katsifis, A & Keller, PA 2023, 'Synthesis and structure-activity relationship (SAR) studies of 1,2,3-triazole, amide, and ester-based benzothiazole derivatives as potential molecular probes for tau protein', RSC Medicinal Chemistry, vol. 14, no. 5, pp. 858-868. https://doi.org/10.1039/d2md00358a

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AU - Wongso, Hendris

AU - Ono, Maiko

AU - Yamasaki, Tomoteru

AU - Kumata, Katsushi

AU - Higuchi, Makoto

AU - Zhang, Ming Rong

AU - Fulham, Michael J.

AU - Katsifis, Andrew

AU - Keller, Paul A.

PY - 2023/1/27

Y1 - 2023/1/27

N2 - The pyridinyl-butadienyl-benzothiazole (PBB3 15) scaffold was used to develop tau ligands with improved in vitro and in vivo properties for imaging applications to provide insights into the etiology and characteristics of Alzheimer's disease. The photoisomerisable trans-butadiene bridge of PBB3 was replaced with 1,2,3-triazole, amide, and ester moieties and in vitro fluorescence staining studies revealed that triazole derivatives showed good visualisation of Aβ plaques, but failed to detect the neurofibrillary tangles (NFTs) in human brain sections. However, NFTs could be observed using the amide 110 and ester 129. Furthermore, the ligands showed low to high affinities (Ki = >1.5 mM-0.46 nM) at the shared binding site(s) with PBB3.

AB - The pyridinyl-butadienyl-benzothiazole (PBB3 15) scaffold was used to develop tau ligands with improved in vitro and in vivo properties for imaging applications to provide insights into the etiology and characteristics of Alzheimer's disease. The photoisomerisable trans-butadiene bridge of PBB3 was replaced with 1,2,3-triazole, amide, and ester moieties and in vitro fluorescence staining studies revealed that triazole derivatives showed good visualisation of Aβ plaques, but failed to detect the neurofibrillary tangles (NFTs) in human brain sections. However, NFTs could be observed using the amide 110 and ester 129. Furthermore, the ligands showed low to high affinities (Ki = >1.5 mM-0.46 nM) at the shared binding site(s) with PBB3.

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Synthesis and structure-activity relationship (SAR) studies of 1,2,3-triazole, amide, and ester-based benzothiazole derivatives as potential molecular probes for tau protein

Abstract

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