Development of Novel Pt(IV)-Carbohydrate Derivatives as Targeted Anticancer Agents against Osteosarcoma.
Int J Mol Sci
; 24(7)2023 Mar 23.
Article
in En
| MEDLINE
| ID: mdl-37047001
ABSTRACT
Despite the enormous importance of cisplatin as a chemotherapeutic agent, its application is impacted by dose-limiting side effects and lack of selectivity for cancer cells. Researchers can overcome these issues by taking advantage of the pro-drug nature of the platinum(IV) oxidation state, and by modifying the coordination sphere of the metal centre with specific vectors whose receptors are overexpressed in tumour cell membranes (e.g., carbohydrates). In this paper we report the synthesis of four novel carbohydrate-modified Pt(IV) pro-drugs, based on the cisplatin scaffold, and their biological activity against osteosarcoma (OS), a malignant tumour which is most common in adolescents and young adults. The carbohydrate-targeting vectors and Pt scaffold are linked using copper-catalysed azide-alkyne cycloaddition (CuAAC) chemistry, which is synonymous with mild and robust reaction conditions. The novel complexes are characterised using multinuclear 1D-2D NMR (1H, 13C and 195Pt), IR, HR-MS, Elem. Analyses, and CV. Cytotoxicity on 2D and 3D and cell morphology studies on OS cell lines, as well as non-cancerous human foetal osteoblasts (hFOBs), are discussed.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Bone Neoplasms
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Prodrugs
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Osteosarcoma
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Coordination Complexes
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Antineoplastic Agents
Limits:
Adolescent
/
Humans
Language:
En
Journal:
Int J Mol Sci
Year:
2023
Document type:
Article
Affiliation country: