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Your search keyword '"Akkaya, Engin U."' showing total 169 results
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169 results on '"Akkaya, Engin U."'

1. Overcoming multidrug resistance by a singlet oxygen releasing camptothecin-endoperoxide.

Author

Zhang, Guangyu, Wang, Lei, Qiao, Yuan, Zhang, Feiyan, Sun, Rensong, and Akkaya, Engin U.

Abstract

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]

Published
2024
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2. Reversing Reprogramming of Cancer Cell Metabolism by Singlet Oxygen Triggered Release of Dichloroacetate Enhances Photodynamic Cytotoxicity.

Author

Zhou, Zhenyan, Wang, Lei, Yan, Shoucai, Liu, Ziang, Sun, Rensong, Qiao, Yuan, and Akkaya, Engin U.

Subjects
REACTIVE oxygen species, CELL metabolism, GLUCOSE metabolism, CYTOTOXINS, ENZYME inhibitors
Abstract

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]

Published
2024
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3. N‐Phenyl‐2‐Pyridone‐Derived Endoperoxide Suppressing both Lung Cancer and Idiopathic Pulmonary Fibrosis Progression by Three‐Pronged Action**.

Author

Wang, Lei, Wu, Hao, Liu, Ziang, Sun, Rensong, Li, Yanping, Si, Yu, Nie, Yun, Qiao, Yuan, Qian, Xiao, Zhang, Shengli, Li, Guangzhe, Sun, Wen, Pan, Yue, and Akkaya, Engin U.

Subjects
IDIOPATHIC pulmonary fibrosis, REACTIVE oxygen species, TRANSFORMING growth factors, PULMONARY fibrosis, LUNG cancer
Abstract

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]

Published
2024
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4. Targeted Endoperoxides Delivering Singlet Oxygen to Cancer Cell Mitochondria: Exploration of the Therapeutic Potential.

Author

Liu, Ziang, Wang, Lei, Sun, Rensong, Wu, Hao, Wang, Yang, Zhang, Shengli, Li, Guangzhe, Shao, Kun, and Akkaya, Engin U.

Subjects
REACTIVE oxygen species, PHOTODYNAMIC therapy, CANCER cells, CELL death, CANCER treatment
Abstract

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]

Published
2024
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5. Self-reporting intracellular delivery agent for singlet oxygen.

Author

Li, Yiran, Wang, Lei, Zhang, Shengli, Liu, Ziang, Sun, Rensong, Qiao, Yuan, and Akkaya, Engin U.

Subjects
CANCER cell culture, CYTOTOXINS, CYCLOELIMINATION reactions, PHENAZINE
Abstract

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]

Published
2024
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36. Catalytic Conversion of Lipophilic Substrates by Phase constrained Enzymes in the Aqueous or in the Membrane Phase

Author

Cebula, Marcus, primary, Turan, Ilke Simsek, additional, Sjödin, Birgitta, additional, Thulasingam, Madhuranayaki, additional, Brock, Joseph, additional, Chmyrov, Volodymyr, additional, Widengren, Jerker, additional, Abe, Hiroshi, additional, Mannervik, Bengt, additional, Haeggström, Jesper Z., additional, Rinaldo-Matthis, Agnes, additional, Akkaya, Engin U., additional, and Morgenstern, Ralf, additional

Published
2016
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37. Catalytic Conversion of Lipophilic Substrates by Phase constrained Enzymes in the Aqueous or in the Membrane Phase

Author

Cebula, Marcus, Turan, Ilke Simsek, Sjodin, Birgitta, Thulasingam, Madhuranayaki, Brock, Joseph, Chmyrov, Volodymyr, Widengren, Jerker, Abe, Hiroshi, Mannervik, Bengt, Haeggstrom, Jesper Z., Rinaldo-Matthis, Agnes, Akkaya, Engin U., Morgenstern, Ralf, Cebula, Marcus, Turan, Ilke Simsek, Sjodin, Birgitta, Thulasingam, Madhuranayaki, Brock, Joseph, Chmyrov, Volodymyr, Widengren, Jerker, Abe, Hiroshi, Mannervik, Bengt, Haeggstrom, Jesper Z., Rinaldo-Matthis, Agnes, Akkaya, Engin U., and Morgenstern, Ralf

Abstract

Both soluble and membrane-bound enzymes can catalyze the conversion of lipophilic substrates. The precise substrate access path, with regard to phase, has however, until now relied on conjecture from enzyme structural data only (certainly giving credible and valuable hypotheses). Alternative methods have been missing. To obtain the first experimental evidence directly determining the access paths (of lipophilic substrates) to phase constrained enzymes we here describe the application of a BODIPY-derived substrate (PS1). Using this tool, which is not accessible to cytosolic enzymes in the presence of detergent and, by contrast, not accessible to membrane embedded enzymes in the absence of detergent, we demonstrate that cytosolic and microsomal glutathione transferases (GSTs), both catalyzing the activation of PS1, do so only within their respective phases. This approach can serve as a guideline to experimentally validate substrate access paths, a fundamental property of phase restricted enzymes. Examples of other enzyme classes with members in both phases are xenobiotic-metabolizing sulphotransferases/UDP-glucuronosyl transferases or epoxide hydrolases. Since specific GSTs have been suggested to contribute to tumor drug resistance, PS1 can also be utilized as a tool to discriminate between phase constrained members of these enzymes by analyzing samples in the absence and presence of Triton X-100., QC 20170119

Published
2016
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41. Cover Picture: Intracellular Modulation of Excited-State Dynamics in a Chromophore Dyad: Differential Enhancement of Photocytotoxicity Targeting Cancer Cells (Angew. Chem. Int. Ed. 18/2015)

Author

Kolemen, Safacan, primary, Işık, Murat, additional, Kim, Gyoung Mi, additional, Kim, Dabin, additional, Geng, Hao, additional, Buyuktemiz, Muhammed, additional, Karatas, Tugce, additional, Zhang, Xian-Fu, additional, Dede, Yavuz, additional, Yoon, Juyoung, additional, and Akkaya, Engin U., additional

Published
2015
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42. Titelbild: Intracellular Modulation of Excited‐State Dynamics in a Chromophore Dyad: Differential Enhancement of Photocytotoxicity Targeting Cancer Cells (Angew. Chem. 18/2015)

Author

Kolemen, Safacan, primary, Işık, Murat, additional, Kim, Gyoung Mi, additional, Kim, Dabin, additional, Geng, Hao, additional, Buyuktemiz, Muhammed, additional, Karatas, Tugce, additional, Zhang, Xian‐Fu, additional, Dede, Yavuz, additional, Yoon, Juyoung, additional, and Akkaya, Engin U., additional

Published
2015
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43. Intracellular Modulation of Excited-State Dynamics in a Chromophore Dyad: Differential Enhancement of Photocytotoxicity Targeting Cancer Cells

Author

Kolemen, Safacan, primary, Işık, Murat, additional, Kim, Gyoung Mi, additional, Kim, Dabin, additional, Geng, Hao, additional, Buyuktemiz, Muhammed, additional, Karatas, Tugce, additional, Zhang, Xian-Fu, additional, Dede, Yavuz, additional, Yoon, Juyoung, additional, and Akkaya, Engin U., additional

Published
2015
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46. Activatable Photosensitizers: Agents for Selective Photodynamic Therapy.

Author

Li, Xingshu, Kolemen, Safacan, Yoon, Juyoung, and Akkaya, Engin U.

Subjects
PHOTOSENSITIZERS, PHOTODYNAMIC therapy, EXCITED state energies, PORPHYRINS spectra, COMPANION diagnostics, REACTIVE oxygen species
Abstract

Recent developments in the design of bifunctional and activatable photosensitizers rejuvenate the aging field of photodynamic sensitization and photodynamic therapy. While systematic studies have uncovered new dyes that can serve as potential photosensitizers, the most promising results have come from studies aimed at gaining precise control over the location and rate of cytotoxic singlet oxygen generation. As a consequence, higher selectivities and efficiencies in photodynamic treatment protocols are now within reach. This feature article highlights the variety of approaches that have been pursued to improve photodynamic therapy and to transform simple photosensitizers into smarter theranostic agents. [ABSTRACT FROM AUTHOR]

Published
2017
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49. Orthogonal Bodipy Trimers as Photosensitizers for Photodynamic Action

Author

Fazli Sozmen, Engin U. Akkaya, José L. Bila, Leyla Tatar Yıldırım, Tugba Ozdemir, [Ozdemir, Tugba -- Akkaya, Engin U.] Bilkent Univ, UNAM Natl Nanotechnol Res Ctr, TR-06800 Ankara, Turkey -- [Bila, Jose Luis -- Akkaya, Engin U.] Bilkent Univ, Dept Chem, TR-06800 Ankara, Turkey -- [Sozmen, Fazli] Cumhuriyet Univ, Dept Nanotechnol Engn, TR-58140 Sivas, Turkey -- [Yildirim, Leyla T.] Hacettepe Univ, Dept Engn Phys, TR-06800 Ankara, Turkey -- [Bila, Jose Luis] EPFL SB ISIC LCS BCH 3409 Batochime UNIL, Av FA Forel 2, CH-1015 Lausanne, Switzerland, Akkaya, Engin -- 0000-0003-4720-7554, and Akkaya, Engin U. -- 0000-0003-4720-7554

Subjects
Diffraction, 010405 organic chemistry, Singlet oxygen, Organic Chemistry, 010402 general chemistry, Photochemistry, 01 natural sciences, Biochemistry, 0104 chemical sciences, chemistry.chemical_compound, Intersystem crossing, chemistry, Physical and Theoretical Chemistry, BODIPY, Absorption (electromagnetic radiation)
Abstract

WOS: 000385053900017, PubMed ID: 27712079, Orthogonally linked BODIPY units shale exceptional intersystem crossing efficiencies. We now report orthogonal BODIPY trimers with strong absorption in the visible region and high singlet oxygen generation capability. The X-ray diffraction structure confirms that the two peripheral BODIPY units are at a perpendicular angle to the core structure., Bilkent University, Financial support by Bilkent University in the form of a graduate student scholarship to J.L.B. is gratefully acknowledged.

Published
2016

50. 'Off–on' switching of intracellular singlet oxygen release under biocompatible conditions

Author

Engin U. Akkaya, Dongmei Xi, Cansu Kaya, Ozlem Seven, Xiaojun Peng, Esma Ucar, Wen Sun, Uçar, Esma, Seven, Özlem, Cansu, Cansu, and Akkaya, Engin U.

Subjects
inorganic chemicals, Cell Survival, medicine.medical_treatment, Biocompatible Materials, Photodynamic therapy, Naphthalenes, 010402 general chemistry, Photochemistry, 01 natural sciences, Catalysis, Fluorides, chemistry.chemical_compound, On demand, Materials Chemistry, medicine, Humans, Microscopy, Confocal, Singlet Oxygen, 010405 organic chemistry, Chemistry, Singlet oxygen, Temperature, Metals and Alloys, Rational design, General Chemistry, Biocompatible material, 0104 chemical sciences, Surfaces, Coatings and Films, Electronic, Optical and Magnetic Materials, Quaternary Ammonium Compounds, MCF-7 Cells, Ceramics and Composites, Fluoride, Intracellular
Abstract

Precise spatiotemporal control of singlet oxygen generation is of immense importance considering its involvement in photodynamic therapy. In this work, we present a rational design for an endoperoxide which is highly stable at ambient temperatures yet, can rapidly be converted into a highly labile endoperoxide, thus releasing the "stored" singlet oxygen on demand. The "off-on" chemical switching from the stable to the labile form is accomplished by the reaction with fluoride ions. The potential utility of controlled singlet oxygen release was demonstrated in cell cultures.

Published
2019

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