UB researchers develop a new family of photoactivatable anticancer metal complexes photoactivatable

The photoswitchable forms of the compounds designed by UB researchers exhibit distinct DNA-interacting and cytotoxic properties, which may lead to a new class of potential photoactivatable anticancer agents.
The photoswitchable forms of the compounds designed by UB researchers exhibit distinct DNA-interacting and cytotoxic properties, which may lead to a new class of potential photoactivatable anticancer agents.
Research
(19/03/2015)

The photoactivation of potential anticancer metal complexes is a topical scientific question as it may lead to the development of more selective drugs. Photoactivated chemotherapy (PACT) with coordination compounds is usually based on a (photo) chemical reaction taking place at the metal centre. Patrick Gamez, ICREA research professor who leads the Bio-Inorganic Chemistry Research Group (QBI) of the University of Barcelona (UB), coordinates a study that has developed a new family of photoactivatable cytotoxic molecules of platinum(II) complexes. Researchers in the Department of Pathology and Experimental Therapeutics of the UB, the Material Science Institute of Aragon (ICMA) and the University of Aveiro (Portugal) also participate in the study.

Platinum complexes have been proven successful as metal-based anticancer drugs. One major drawback of chemotherapy is the development of unpleasant treatment related side effects, which are due to the poor selectivity of the therapeutic agents. The coordination compounds described in the study present two photoisomers that interact differently with DNA duplex. “Even more interesting is the fact that each isomer exhibits a different cytotoxic behaviour against various cancer cell lines, one of them being notably more active than the other”, emphasizes Gamez.

Study results, published in the scientific journal Angewandte Chemie, provide new insight into the field of PACT. “We are currently preparing new members of this new category of molecules, and the study of the effect of the photoswitching process inside cells is being set up”, affirms Gamez. Researchers are exploiting a new strategy that consists of “photomodifying” a ligand coordinated to metal ions. They have prepared platinum(II) complexes from photoswitchable ligands, which exhibit two inter-convertible photoisomeric forms that present distinct DNA-interacting properties and cytotoxic behaviours.

 

Article reference:

Presa, A.; Brissos, R. F.; Caballero, A. B.; Borilovic, I.; Korrodi-Gregório, L.; Pérez-Tomás, R.; Roubeau, O.; Gamez, P. “Photoswitching the Cytotoxic Properties of Platinum(II) Compounds”. Angewandte Chemie, January 2015. DOI: 10.1002/anie.201412157

 

The photoswitchable forms of the compounds designed by UB researchers exhibit distinct DNA-interacting and cytotoxic properties, which may lead to a new class of potential photoactivatable anticancer agents.
The photoswitchable forms of the compounds designed by UB researchers exhibit distinct DNA-interacting and cytotoxic properties, which may lead to a new class of potential photoactivatable anticancer agents.
Research
19/03/2015

The photoactivation of potential anticancer metal complexes is a topical scientific question as it may lead to the development of more selective drugs. Photoactivated chemotherapy (PACT) with coordination compounds is usually based on a (photo) chemical reaction taking place at the metal centre. Patrick Gamez, ICREA research professor who leads the Bio-Inorganic Chemistry Research Group (QBI) of the University of Barcelona (UB), coordinates a study that has developed a new family of photoactivatable cytotoxic molecules of platinum(II) complexes. Researchers in the Department of Pathology and Experimental Therapeutics of the UB, the Material Science Institute of Aragon (ICMA) and the University of Aveiro (Portugal) also participate in the study.

Platinum complexes have been proven successful as metal-based anticancer drugs. One major drawback of chemotherapy is the development of unpleasant treatment related side effects, which are due to the poor selectivity of the therapeutic agents. The coordination compounds described in the study present two photoisomers that interact differently with DNA duplex. “Even more interesting is the fact that each isomer exhibits a different cytotoxic behaviour against various cancer cell lines, one of them being notably more active than the other”, emphasizes Gamez.

Study results, published in the scientific journal Angewandte Chemie, provide new insight into the field of PACT. “We are currently preparing new members of this new category of molecules, and the study of the effect of the photoswitching process inside cells is being set up”, affirms Gamez. Researchers are exploiting a new strategy that consists of “photomodifying” a ligand coordinated to metal ions. They have prepared platinum(II) complexes from photoswitchable ligands, which exhibit two inter-convertible photoisomeric forms that present distinct DNA-interacting properties and cytotoxic behaviours.

 

Article reference:

Presa, A.; Brissos, R. F.; Caballero, A. B.; Borilovic, I.; Korrodi-Gregório, L.; Pérez-Tomás, R.; Roubeau, O.; Gamez, P. “Photoswitching the Cytotoxic Properties of Platinum(II) Compounds”. Angewandte Chemie, January 2015. DOI: 10.1002/anie.201412157

 

En lʼestudi també hi han participat investigadors del Departament de Patologia i Terapèutica Experimental de la UB, de lʼInstitut de Ciència de Materials dʼAragó (ICMA) i de la Universitat dʼAveiro (Portugal).

Un dels grans inconvenients de la quimioteràpia són els efectes secundaris, tan desagradables, com a conseqüència de lʼescassa selectivitat dels agents terapèutics. Els compostos de coordinació que descriu lʼestudi dirigit pel professor Gámez presenten dos fotoisòmers que interactuen de manera diferent amb la doble hèlix de lʼADN. «Un dels aspectes més interessants és que cada isòmer presenta un comportament citotòxic diferent davant diverses línies cel·lulars de càncer, i una dʼelles és molt més activa que lʼaltra», subratlla Gámez.

Els resultats de lʼestudi, publicat per la revista científica Angewandte Chemie, obren noves línies de recerca en quimioteràpia. «Actualment, estem treballant en el desenvolupament de compostos nous dins dʼaquesta nova categoria de molècules; a més, acabem de començar a analitzar els efectes del procés de fotocommutació a lʼinterior de la cèl·lula», afirma Gámez. El grup dʼinvestigadors està desenvolupant una nova estratègia que consisteix a «fotomodificar» el lligand que uneix els ions metàl·lics. Els investigadors han creat complexos de platí a partir de lligands fotocommutables que presenten dues formes fotoisomèriques interconvertibles amb diferents propietats dʼinteracció amb lʼADN i comportaments citotòxics.

 

Article:

Presa, A.; Brissos, R. F; Caballero, A. B.; Borilovic, I.; Korrodi-Gregório, L.; Pérez-Tomás, R.; Roubeau, O.; Gamez, P. «Photoswitching the cytotoxic properties of platinum (II) compounds». Angewandte Chemie, gener de 2015.DOI: 10.1002/anie.201412157