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Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents
Published on: May 28, 2014
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Cytotoxic trans-platinum(II) complex with 3-hydroxymethylpyridine: Synthesis, X-ray structure and biological activity
Sabina Grabner1, Barbara Modec1, Nataša Bukovec1
1Faculty of Chemistry and Chemical Technology, University of Ljubljana, Večna pot 113, SI-1000 Ljubljana, Slovenia.
Journal of Inorganic Biochemistry
|May 19, 2016
Summary
Novel platinum(II) complexes with 3-hydroxymethylpyridine (3-hmpy) show potent anticancer activity. Compound 2, a transplatin analogue, demonstrated comparable efficacy to cisplatin in preclinical models, with improved safety profiles.
Area of Science:
- Inorganic Chemistry
- Medicinal Chemistry
- Cancer Biology
Background:
- Platinum(II) complexes are vital in cancer chemotherapy.
- Developing novel platinum analogues with improved efficacy and reduced toxicity is crucial.
- 3-hydroxymethylpyridine (3-hmpy) was investigated as a carrier ligand for Pt(II) complexes.
Purpose of the Study:
- To synthesize and characterize novel Pt(II) complexes with 3-hmpy.
- To evaluate the cytostatic and cytotoxic properties of these complexes against cancer cell lines.
- To compare the efficacy and safety of the most potent compound with cisplatin in preclinical models.
Main Methods:
- Synthesis and structural characterization of cis- and trans-[PtCl2(3-hmpy)2] complexes using elemental analysis, FTIR, NMR, and X-ray crystallography.
- In vitro cytotoxicity assessment using MTT and clonogenic assays on T24 human bladder carcinoma cells.
- Evaluation of compound 2 in cisplatin-sensitive (IGROV 1) and resistant (IGROV 1/RDDP) human ovarian carcinoma cell lines.
- Analysis of DNA conformational changes, apoptosis induction, and platinum levels in tumors and serum.
- In vivo antitumour efficacy studies and body weight monitoring in animal models.
Main Results:
- Two novel Pt(II) complexes, cis-[PtCl2(3-hmpy)2] (1) and trans-[PtCl2(3-hmpy)2] (2), were successfully synthesized and characterized.
- Compound 2 exhibited significant cytotoxicity against T24 cells and demonstrated comparable efficacy to cisplatin in cisplatin-resistant ovarian cancer cells (IGROV 1/RDDP).
- Compound 2 induced DNA conformational changes, delayed apoptosis in T24 cells, and showed higher platinum accumulation in tumors and serum compared to cisplatin.
- In vivo studies revealed that compound 2 possessed comparable antitumour effectiveness to cisplatin with a reduced impact on animal body weight.
Conclusions:
- The transplatin analogue, compound 2, displays promising anticancer properties with potential for improved therapeutic index.
- Compound 2's ability to overcome cisplatin resistance and its favorable in vivo profile warrant further investigation as a potential chemotherapeutic agent.
