Data · dataset · 2026
Scorpion-Inspired 1,3,4-Oxadiazole-Based GSK-3β-Targeting Agents: Design, Synthesis, and Biological Evaluation
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<p>Glycogen synthase kinase-3β (GSK-3β) is a promising therapeutic target for anticancer drug development because it is involved in cell proliferation, apoptosis, and tumor progression.
Description
However, developing structurally distinct GSK-3β-directed anticancer scaffolds with favorable cancer-cell selectivity remains challenging. In this study, 10 scorpion-inspired 2-(phenacylthio)-1,3,4-oxadiazole derivatives (<b>ODS1-10</b>) were synthesized in 65–97% yields and evaluated for their anticancer potential.
Among the synthesized compounds, <b>ODS-7</b> showed the highest activity against MDA-MB-231 cells (IC<sub>50</sub> = 32.7 μM), whereas <b>ODS-5</b> was the most active derivative against SH-SY5Y cells (IC<sub>50</sub> = 21.2 μM). Structure–activity relationship analysis indicated that the electronic properties and substitution pattern of the aryl moieties substantially influenced antiproliferative activity. <b>ODS-5</b> and <b>ODS-7</b> showed preferential activity toward cancer cells, with <b>ODS-5</b> exhibiting a selectivity index of 2.80 against non-cancerous HaCaT keratinocytes.
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Both compounds significantly reduced SH-SY5Y clonogenic capacity and disrupted three-dimensional spheroid integrity. Immunofluorescence analysis revealed reduced GSK-3β-associated fluorescence intensity in treated SH-SY5Y cells, while RT-qPCR demonstrated upregulation of BAX and CASP3 and downregulation of BCL2, supporting the involvement of apoptosis in the observed cytotoxic response. Molecular docking also showed favorable predicted binding energies for <b>ODS-5</b> (−8.67 kcal/mol) and <b>ODS-7</b> (−8.44 kcal/mol) within the GSK-3β binding site, comparable to the co-crystallized ligand 3HT (−8.37 kcal/mol).
Overall, <b>ODS-5</b> and <b>ODS-7</b> represent promising preliminary lead structures within the 2-(phenacylthio)-1,3,4-oxadiazole series, providing a rational SAR basis for further medicinal chemistry optimization and direct evaluation of GSK-3β target engagement.</p> <p>Multi-panel diagram depicting a scorpion-inspired design, synthesized derivatives, target engagement with GSK-3ß, and mechanistic marker results.</p>
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Where it is published
- DOI doi.org/10.6084/m9.figshare.34021673.v1 ↗
DOI / persistent id · from zivahub uct ac za
Catalogue records · 1
- OAI-PMH record api.figshare.com/v2/oai?verb=GetRecord&metadataPrefix=oai_dc&identifier=oai%3Af… ↗
metadata API · from zivahub uct ac za
Topics
- From keywords
- Biochemistry and cell biology · Cancer · Chemistry · Earth & Environmental Science · Immunology · Life Sciences · Medicine & Health
Provenance · 1 source records, 12 field assertions
| Source | Key | Last seen | Raw |
|---|---|---|---|
| ZivaHub | oai:figshare.com:article/34021673 | 13 d ago | JSON v1 |
| Field | Assertion | Extractor | Evidence |
|---|---|---|---|
| access_level | source · zivahub uct ac za | connector:zivahub_uct_ac_za@1.0.0 | |
| concepts[disease].local:disease:cancer | mapping · zivahub uct ac za | vocabulary-mapper@1.0.0 | keywords['Cancer'] |
| concepts[field].anzsrc:group:3101 | mapping · zivahub uct ac za | vocabulary-mapper@1.0.0 | keywords['Cell Biology'] |
| concepts[field].anzsrc:group:3204 | mapping · zivahub uct ac za | vocabulary-mapper@1.0.0 | keywords['Immunology'] |
| concepts[field].local:field:chemistry | mapping · zivahub uct ac za | connector:zivahub_uct_ac_za@1.0.0 | |
| concepts[field].local:field:earth-environmental | mapping · zivahub uct ac za | connector:zivahub_uct_ac_za@1.0.0 | |
| concepts[field].local:field:life-sciences | mapping · zivahub uct ac za | connector:zivahub_uct_ac_za@1.0.0 | |
| concepts[field].local:field:medicine-health | mapping · zivahub uct ac za | connector:zivahub_uct_ac_za@1.0.0 | |
| description | source · zivahub uct ac za | connector:zivahub_uct_ac_za@1.0.0 | /metadata/dc/description |
| license | source · zivahub uct ac za | connector:zivahub_uct_ac_za@1.0.0 | /metadata/dc/rights |
| publication_date | source · zivahub uct ac za | connector:zivahub_uct_ac_za@1.0.0 | |
| title | source · zivahub uct ac za | connector:zivahub_uct_ac_za@1.0.0 | /metadata/dc/title |