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Effect of Regiochemistry and Methylation on the Anticancer Activity of a Ferrocene-Containing Organometallic Nucleoside Analogue.
- Source :
-
Chembiochem : a European journal of chemical biology [Chembiochem] 2020 Sep 01; Vol. 21 (17), pp. 2487-2494. Date of Electronic Publication: 2020 May 19. - Publication Year :
- 2020
-
Abstract
- Four new bis-substituted ferrocene derivatives containing either a hydroxyalkyl or methoxyalkyl group and either a thyminyl or methylthyminyl group have been synthesised and characterised by a range of spectroscopic and analytical techniques. They were included in a structure-activity-relationship (SAR) study probing anticancer activities in osteosarcoma (bone cancer) cell lines and were compared with a known lead compound, 1-(S,R <subscript>p</subscript> ), a nucleoside analogue that is highly toxic to cancer cells. Biological studies using the MTT assay revealed that a regioisomer of ferronucleoside 1-(S,R <subscript>p</subscript> ), which only differs from the lead compound in being substituted on two cyclopentadienyl rings rather than one, was over 20 times less cytotoxic. On the other hand, methylated derivatives of 1-(S,R <subscript>p</subscript> ) showed comparable cytotoxicities to the lead compound. Overall these studies indicate that a mechanism of action for 1-(S,R <subscript>p</subscript> ) cannot proceed through alcohol phosphorylation and that its geometry and size, rather than any particular functional group, are crucial factors in explaining its high anticancer activity.<br /> (© 2020 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Subjects :
- Antineoplastic Agents chemical synthesis
Antineoplastic Agents chemistry
Bone Neoplasms pathology
Cell Proliferation drug effects
Cell Survival drug effects
Crystallography, X-Ray
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Ferrous Compounds chemistry
Humans
Metallocenes chemistry
Methylation
Models, Molecular
Molecular Structure
Nucleosides chemistry
Organometallic Compounds chemical synthesis
Organometallic Compounds chemistry
Osteosarcoma pathology
Structure-Activity Relationship
Tumor Cells, Cultured
Antineoplastic Agents pharmacology
Bone Neoplasms drug therapy
Ferrous Compounds pharmacology
Metallocenes pharmacology
Nucleosides pharmacology
Organometallic Compounds pharmacology
Osteosarcoma drug therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1439-7633
- Volume :
- 21
- Issue :
- 17
- Database :
- MEDLINE
- Journal :
- Chembiochem : a European journal of chemical biology
- Publication Type :
- Academic Journal
- Accession number :
- 32255248
- Full Text :
- https://doi.org/10.1002/cbic.202000124