Abstract
We here report our studies on the reaction with the platinum(II) ion of a nucleoamino acid constituted by the l-2,3-diaminopropanoic acid linked to the thymine nucleobase through a methylenecarbonyl linker. The obtained new platinum complexes, characterized by spectroscopic and mass spectrometric techniques, were envisaged to exploit synergistic effects due to the presence of both the platinum center and the nucleoamino acid moiety. The latter can be potentially useful to protect the complexes from early deactivation, as well as to facilitate their cell internalization. The biological activity of the complexes in terms of antiproliferative effects was evaluated in vitro on different cancer cell lines and healthy cells, showing the best results on human cervical adenocarcinoma (HeLa) cells along with good selectivity for cancer over normal cells. In contrast, the metal-free nucleoamino acid did not show any cytotoxicity on both normal and cancer cell lines. Finally, the ability of the novel Pt(II) complexes to bind various DNA model systems was investigated by circular dichroism (CD) spectroscopy and polyacrylamide gel electrophoresis analyses proving that the newly obtained compounds can potentially target DNA, similarly to other well-known anticancer Pt complexes, with a peculiar G-quadruplex vs. duplex selectivity.
Highlights
Cisplatin is one of the most active chemotherapeutic agents used for the treatment of a large variety of malignancies, especially testicular and ovarian carcinomas, even if its clinical utility is restricted by both toxicological and tumor resistance drawbacks [1,2].CDDP activity and toxicity is mainly due to DNA binding [3,4], occurring via both inter- and intrastrand crosslinks, that suppresses DNA replication and RNA transcription
The final deprotected nucleoamino acid 4 was purified by high-performance liquid-chromatography (HPLC) and characterized by mass spectrometry (MS), i.e., matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) and liquid chromatography-electrospray ionization (LC-ESI) MS (Figure S1), and nuclear magnetic resonance (NMR) spectroscopy (Figures S2 and S3), which in all cases confirmed the identity and purity of the target compound
The identity of the new metal complexes was ascertained by NMR spectroscopy (1 H and 13 C, correlation spectroscopy (COSY), heteronuclear single quantum correlation (HSQC), heteronuclear multiple-bond correlation (HMBC), and NOESY experiments) and mass spectrometry (LC-ESI-MS) techniques
Summary
Cisplatin (cis-diaminedichloro-platinum, CDDP) is one of the most active chemotherapeutic agents used for the treatment of a large variety of malignancies, especially testicular and ovarian carcinomas, even if its clinical utility is restricted by both toxicological and tumor resistance drawbacks [1,2].CDDP activity and toxicity is mainly due to DNA binding [3,4], occurring via both inter- and intrastrand crosslinks, that suppresses DNA replication and RNA transcription. The drawbacks and side effects of cisplatin treatment [1,2] have stimulated the design and synthesis of new anticancer Pt-based drugs with the aim of obtaining compounds more effective and Pharmaceuticals 2020, 13, 284; doi:10.3390/ph13100284 www.mdpi.com/journal/pharmaceuticals. The drawbacks and side effects of cisplatin treatment [1,2] have stimulated the design of and synthesis of new anticancer Pt-based drugs with the aim of obtaining compounds more effective and less toxic than CDDP. In the last decades, a wide variety of Pt complexes have been tested for less toxic than CDDP. In the lasthave decades, wide variety of Pttrials, complexes have testedbeen for antiproliferative activity [5,6,7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
