Toxicity assessments and transcriptional effects of monofunctionalized Pt(II) complex under dark and light irradiation condition in Caenorhabditis elegans

Computational Analysis of the Behavior of BODIPY Decorated Monofunctional Platinum(II) Complexes in the Dark and under Light Irradiation

“…From a comparison between the values obtained for dCBP and its parent Pyrim , it appears that the presence of the appended BODIPY does not play a significant role at this stage and the more sterically hindered structure of the binuclear Pt complex, regardless the presence of the BODIPY moiety, penalizes the second guanine attack. According to the enhanced experimentally observed loss of DNA helical structure for dCBP , , it can be inferred from such results that, in analogy to phenanthriplatin, , the first attack to a guanine base causes an initial DNA double helix distortion. Such a distortion could lead to a rearrangement of the real DNA flexible structure more favorable to the second guanine attack and, therefore, to cross-linking.…”

“…Unlike cisplatin, nonetheless, only a single bond can be formed with DNA, as in such drugs only one labile ligand is bound to the metal center, and due to additional interactions and steric hindrance, cellular repair ability via transcription is reduced and apoptosis is induced with a different mechanism. , Aiming at enhancing the efficacy of monofunctional anticancer agents, dual-action complexes have been designed by appending a suitable photosensitizer (PS) to the ligand bound to platinum­(II). Two-component systems of this kind have recently received increasing attention due to the possibility to combine the DNA cross-linking ability of the complex bearing a labile anionic ligand, generally a chloride, with the photodynamic therapy (PDT) effect of a PS. − PDT is an alternative treatment for the control of malignant diseases based on the uptake of a photosensitizing molecule which, upon being excited by light of proper wavelength, reacts with oxygen and generates oxidant species in target tissues, leading to cell death. , The PS, in the photodynamic process, is promoted from its ground singlet state to an excited one. The excitation is followed by an intersystem crossing (ISC) transition to a lower triplet state, being a usually forbidden nonradiative process that can take place if the relativistic spin–orbit coupling (SOC) between the two states is large enough and the involved states are close in energy to permit the process to be efficient.…”

“…Given such premises and due to the prominent place that dual-action drugs are occupying in the scientific landscape of cancer research thanks to the possibility to combine different therapeutic strategies within one molecule, we have carefully examined both the photophysical properties and the key steps of the mechanism of action of two BODIPY-appended monofunctional Pt­(II) complexes recently synthesized and tested for their cytotoxicity. , The structures of the two investigated complexes named in the original papers mCBP {[ cis -Pt­(NH 3 ) 2 Cl]-8-( p -pyridinemethylene),1,3,5,7-tetramethyldipyrrinborondifluoride} + and dCBP {[ cis -Pt­(NH 3 ) 2 Cl] 2 -8-(1,3-pyrimidine-5-methylene),1,3,5,7-tetramethyldipyrrinborondifluoride} 2+ , are shown in Scheme , with the latter being a binuclear Pt­(II) complex. For both compounds, it is reported that they show promising ROS generating capability under light irradiation reinforcing the classical chemo-therapic action in the dark caused by DNA distortion.…”

“…Two-component systems of this kind have recently received increasing attention due to the possibility to combine the DNA cross-linking ability of the complex bearing a labile anionic ligand, generally a chloride, with the photodynamic therapy (PDT) effect of a PS. 13 − 18 PDT is an alternative treatment for the control of malignant diseases based on the uptake of a photosensitizing molecule which, upon being excited by light of proper wavelength, reacts with oxygen and generates oxidant species in target tissues, leading to cell death. 19 , 20 The PS, in the photodynamic process, is promoted from its ground singlet state to an excited one.…”

Platinum based theranostics nanoplatforms for antitumor applications

“…7 When the photosensitizer is activated by light, it transfers energy to molecular oxygen, generating reactive oxygen species that can damage cellular components and induce cell death. 8 The use of Pt( ii ) complexes as photosensitizers in PDT is an active area of research, as they offer several advantages over traditional photosensitizers, including higher stability and greater water solubility.…”