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We made structural modifications on the A-ring of camptothecin (CPT) by incorporating methyl substituents on positions 9 and 12. This allows conversion of the camptothecin-derivative to an endoperoxide (ENDO-CPT). The endoperoxide obtained this way thermally releases singlet oxygen, reverting back to the original 9,12-dimethylcamptothecin (DM-CPT) with a half-life of 1.4 hours at 37 °C. Endoperoxide modification yields a significant improvement in cytotoxicity against MDR-cell lines, compared to both CPT and DM-CPT. It appears that the simultaneous action of singlet oxygen and CPT is highly effective due to the targeting of P-glycoprotein by singlet oxygen. [ABSTRACT FROM AUTHOR]

Cancer cells change their glucose metabolism towards lactic acid production for various defensive and proliferative advantages. Dichloroacetate (DCA) is an inhibitor of a key enzyme and thus, changes back the OX‐PHOS to glycolysis ratio. We designed and synthesized a singlet oxygen triggered source of dichloroacetate which releases this inhibitor during photodynamic singlet oxygen generation. Synergistic action of DCA and singlet oxygen results in significant enhancement of photocytotoxicity. The results suggest that this approach could offer significant improvement in the therapeutic outcome of PDT. [ABSTRACT FROM AUTHOR]

We report an endoperoxide compound (E5) which can deliver three therapeutic components by a thermal cycloreversion, namely, singlet oxygen, triplet oxygen and 3‐methyl‐N‐phenyl‐2‐pyridone (P5), thus targeting multiple mechanisms for treating non‐small cell lung cancer and idiopathic pulmonary fibrosis. In aqueous environment, E5 undergoes clean reaction to afford three therapeutic components with a half‐life of 8.3 hours without the generation of other by‐products, which not only achieves good cytotoxicity toward lung cancer cells and decreases the levels of hypoxia‐inducible factor 1α (HIF‐1α) protein, but also inhibits the transforming growth factor β1 (TGF‐β1) induced fibrosis in vitro. In vivo experiments also demonstrated the efficacy of E5 in inhibiting tumor growth and relieving idiopathic pulmonary fibrosis, while exhibiting good biocompatibility. Many lines of evidence reveal the therapeutic efficacy of singlet oxygen and 3‐methyl‐N‐phenyl‐2‐pyridone for these two lung diseases, and triplet oxygen could downregulate HIF‐1α and relieve tumor hypoxia which is a critical issue in photodynamic therapy (PDT). Unlike other combination therapies, in which multiple therapeutic agents are given in independent formulations, our work demonstrates single molecule endoperoxide prodrugs could be developed as new platforms for treatment of cancers and related diseases. [ABSTRACT FROM AUTHOR]

The clinical practice of photodynamic therapy of cancer (PDT) is mostly limited to superficial types of cancer. The major reason behind this limited applicability is the need for light in the photogeneration of ROS, and in particular singlet oxygen. In order to circumvent this major roadblock, we designed and synthesized naphthalene‐derived endoperoxides with mitochondria targeting triphenylphosphonium moieties. Here, we show that these compounds release singlet oxygen by thermal cycloreversion, and initiate cell death with IC50<10 μM in cancer cell cultures. The mouse 4T1 breast tumor model study, where the endoperoxide compound was introduced intraperitoneally, also showed highly promising results, with negligible systemic toxicity. Targeted delivery of singlet oxygen to cancer cell mitochondria could be the breakthrough needed to transform Photodynamic Therapy into a broadly applicable methodology for cancer treatment by keeping the central tenet and discarding problematic dependencies on oxygen or external light. [ABSTRACT FROM AUTHOR]

1,4-Dimethylphenazine endoperoxide releases singlet oxygen with a half-life of 89 hours at 37 °C. The thermal cycloreversion reaction is accompanied by a strong increase in the emission intensity with a peak at 490 nm, due to the formation of the phenazine core. The endoperoxide is effective against cancer cells in culture medium and tumor spheroids, with singlet oxygen-mediated cytotoxicity. [ABSTRACT FROM AUTHOR]

The versatile chemistry of Bodipy dyes which facilitates the design and synthesis of multivalent-multitopic derivatives based on the selection of metal ion-ligand pairs to afford photoinduced electron transfer and internal charge transfer processes is reported. The different metal ions with careful design could selectively modulate diverse photophysical processes to result in a range of signals, useful in molecular logic design, and an interesting potential for multianalyte chemosensors.

The consequences of the modulation of energy transfer efficiency at the energy donor site are explored in a molecular design that has an ICT type metal ion-sensitive chromophore placed as the energy donor in the dyad. The studies have shown unaltered emission wavelength in the red end of the visible spectrum, while keeping a large Stokes shift and the ratiometric character.

The process of designing of ratiometric chemosensors requires magnitude of the range of signal ratios of emission intensities at two different wavelengths for the analyte free and analyte bound chemosensor. The feasibility of this approach is demonstrated by synthesizing a series of boradiazaindacene dyads with increasing interchromophoric distance and the specific dithiazacrown selected shows selectivity for Hg(II) ions in a range of solvents.

A general strategy for large pseudo-Stokes' shift, ratiometric chemosensors, utilizing efficient energy transfer is introduced. However, the synthesis is highly straightforward due to the symmetry of the precursor and in only one step, this symmetric precursor can be transformed into an efficient RET system where the choice of the ligand carrying aldehyde would determine the selectivity of the resulting chemosensor.