Revealing the Effect of Host-Guest Complementarity in Supramolecular Monofunctional Platinum(II) Drugs

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F24%3A00137398" target="_blank" >RIV/00216224:14740/24:00137398 - isvavai.cz</a>

Výsledek na webu

<a href="http://dx.doi.org/10.1039/D4QI02012J" target="_blank" >http://dx.doi.org/10.1039/D4QI02012J</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1039/D4QI02012J" target="_blank" >10.1039/D4QI02012J</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Revealing the Effect of Host-Guest Complementarity in Supramolecular Monofunctional Platinum(II) Drugs

Popis výsledku v původním jazyce

Monofunctional platinum(II) compounds bearing planar aromatic ligands can be significantly more potent for the treatment of tumors than the traditional bifunctional platinum(II) systems derived from cisplatin. Their properties can be modulated by using a drug carrier, for example, by trapping them into a macrocyclic cavitand and releasing the metallodrug in a controlled manner. In this work, we introduce new monofunctional platinum(II) compounds with the general structure cis-[PtII(NH3)2Cl(4-R-py)]+NO3- as direct analogs of pyriplatin, cis-[PtII(NH3)2Cl(py)]+. We investigated their chemical activation by aquation in host-guest (HG) complexes with the cucurbit[7]uril (CB7) macrocycle. We used a range of NMR techniques to characterize the HG complexation in detail, and the effects of the ligand on the structure and aquation of chloride at the platinum center in the HG complexes were rationalized with the support of molecular dynamics (MD) simulations and density-functional theory (DFT) calculations. Biological screening of the cytotoxicity and the drug uptake by cell lines A2780 and A2780/CP showed that the cytotoxicity of the Pt-compound with 4-phenylpyridine and 4-pentafluorophenylpyridine ligand was comparable to that of cisplatin and that the cytotoxicity and drug uptake of the Pt-compound with a 4-(1-adamantyl)pyridine ligand was greatly modulated by the CB7 carrier. Our observations indicate great potential for HG complexes in the future supramolecular design and structural tailoring of biological activity.

Název v anglickém jazyce

Revealing the Effect of Host-Guest Complementarity in Supramolecular Monofunctional Platinum(II) Drugs

Popis výsledku anglicky

Monofunctional platinum(II) compounds bearing planar aromatic ligands can be significantly more potent for the treatment of tumors than the traditional bifunctional platinum(II) systems derived from cisplatin. Their properties can be modulated by using a drug carrier, for example, by trapping them into a macrocyclic cavitand and releasing the metallodrug in a controlled manner. In this work, we introduce new monofunctional platinum(II) compounds with the general structure cis-[PtII(NH3)2Cl(4-R-py)]+NO3- as direct analogs of pyriplatin, cis-[PtII(NH3)2Cl(py)]+. We investigated their chemical activation by aquation in host-guest (HG) complexes with the cucurbit[7]uril (CB7) macrocycle. We used a range of NMR techniques to characterize the HG complexation in detail, and the effects of the ligand on the structure and aquation of chloride at the platinum center in the HG complexes were rationalized with the support of molecular dynamics (MD) simulations and density-functional theory (DFT) calculations. Biological screening of the cytotoxicity and the drug uptake by cell lines A2780 and A2780/CP showed that the cytotoxicity of the Pt-compound with 4-phenylpyridine and 4-pentafluorophenylpyridine ligand was comparable to that of cisplatin and that the cytotoxicity and drug uptake of the Pt-compound with a 4-(1-adamantyl)pyridine ligand was greatly modulated by the CB7 carrier. Our observations indicate great potential for HG complexes in the future supramolecular design and structural tailoring of biological activity.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10400 - Chemical sciences

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2024

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Inorganic Chemistry Frontiers

ISSN

2052-1553

e-ISSN

2052-1553

Svazek periodika

11

Číslo periodika v rámci svazku

23

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

16

Strana od-do

8510-8525

Kód UT WoS článku

001344416300001

EID výsledku v databázi Scopus

2-s2.0-85208687206