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Öğe Anti-Cancer and Anti-Inflammatory Activities of Bromo- and Cyano-Substituted Azulene Derivatives(Springer/Plenum Publishers, 2020) Ayaz, Furkan; Yuzer, Abdulcelil; Ince, Tuncay; Ince, MineNatural products and their synthetic derivatives gathered attention due to their pharmaceutical capacities. They have been in use against different types of diseases ranging from cancer to inflammatory disorders. In order to increase their efficacy and prevent the possible side effects, these natural compounds are manipulated at the laboratory conditions and modified according to our needs. Azulene is one of these compounds whose anti-inflammatory potential have been shown by the previous studies, but a detailed analysis of its effect at the cellular level in terms of pro-inflammatory cytokine production has not been studied yet. Moreover, its derivative potential has not been characterized extensively. In our study, we examined the cytotoxic, immunomodulatory and immunostimulatory potential of bromo- and cyano-substituted azulenes on the mammalian macrophages. These unique compounds had differential effects on the production of pro-inflammatory cytokines and they were anti-inflammatory immunomodulators. Furthermore, they exerted anti-proliferative effect on breast and prostate cancer cells which supports their anti-cancer potential as well.Öğe Detection of Kallikrein-Related Peptidase 4 with a Label-free Electrochemical Impedance Biosensor Based on a Zinc(II) Phthalocyanine Tetracarboxylic Acid-Functionalized Disposable Indium Tin Oxide Electrode(Amer Chemical Soc, 2021) Aydin, Elif Burcu; Aydin, Muhammet; Yuzer, Abdulcelil; Ince, Mine; Ocakoglu, Kasim; Sezginturk, Mustafa KemalA new impedimetric biosensing system based on kallikrein-related peptidase 4 (KLK 4) antigen-specific antibodies and a zinc(II) phthalocyanine tetracarboxylic acid (Zn-PcTCa) matrix material was developed for the first time in this study. First, a Zn-PcTCa-coated indium tin oxide surface was used as an interface matrix material for the immobilization of anti-KLK 4 antibodies, and they bound to the platform via amide bonds. In the presence of KLK 4 antigens, the anti-KLK 4 antibodies specifically captured these antigens and caused changes in the electrochemical properties of the system. Randles equivalent circuit was utilized to evaluate the impedimetric signal, which was measured with the help of an electrochemical impedance spectroscopy method. After the specific interaction, the electron transfer resistance (R-ct) was remarkably increased and displayed a linear relationship with the level of the KLK 4 antigen in the range of 0.02-15 pg/mL, with a a detection limit of 6.8 fg/mL. The designed biosensor was able to detect a KLK 4 antigen with good sensitivity, excellent specificity, and high stability. In addition, because of having a low-cost and robust procedure for fabrication, it could be repeatedly used in several areas including clinical diagnosis.Öğe Fabrication and characterization of polyethersulfone membranes functionalized with zinc phthalocyanines embedding different substitute groups(Elsevier, 2021) Bilici, Zeynep; Ozay, Yasin; Yuzer, Abdulcelil; Ince, Mine; Ocakoglu, Kasim; Dizge, NadirIn this study, a novel polyethersulphone (PES) composite membrane incorporated with two different zinc phthalocyanines (ZnPc), tetra-iodo and octa(2,6-diphenylphenoxy), was fabricated through the phase inversion approach. Three different concentrations of zinc phthalocyanines (0.5, 1.0, and 2.0 wt.%) were blended into the PES membrane. The morphology and performance of the fabricated composite membranes were systematically studied by scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy (EDS) mapping, atomic force microscopy (AFM), porosity, water contact angle, antifouling, and rejection measurements. Hydrophobicity of the pristine membrane decreased from 79.67 degrees to 77.03 degrees and from 79.67 degrees to 67.57 degrees after blending of 2.0 wt.% tetra-iodo ZnPc (TI-ZnPc) and octa(2,6-diphenylphenoxy) ZnPc (DP-ZnPc), respectively. Furthermore, the porosity and mean pore radius decreased due to the introducing of ZnPc. Porosity of the pristine membrane decreased from 60.60 % to 44.96 % and 42.21 % after blending of TI-ZnPc and DP-ZnPc, respectively. Mean pore size of the pristine membrane decreased from 22.70 nm to 9.11 nm and 17.93 nm after blending of TIZnPc and DP-ZnPc, respectively. BSA filtration mostly affected the flux of pristine membrane and caused it to decrease from 133.5 to 87.1 L/m(2)h (relative flux reduction (RFR) of 34.7 %). RFR decreased up to 19.2 % and 17.3 % for TI-ZnPc 2.0 wt% and DP-ZnPc 2.0 wt% composite membranes. Pristine PES membrane rejected 45.8 % BSA. However, TI-ZnPc 2.0 wt% and DP-ZnPc 2.0 wt% composite membranes supplied 91.0 % and 70.6 % BSA rejections, respectively. In comparison to pristine PES membrane, the total resistance (R-t) values of the composite membranes decreased. The pristine PES membrane showed the lowest flux recovery ratio (FRR, 71.89 %) against BSA, while all-composite membranes showed promising antifouling properties. FRR increased up to 97.44 % and 89.06 % for TI-ZnPc 2.0 wt% and DP-ZnPc 2.0 wt% composite membranes, respectively. The pristine PES membrane showed the lowest FRR against activated sludge, while all composite membranes showed promising antifouling properties. Moreover, ZnPc-embedded PES composite membranes were irradiated with appropriate wavelengths of light in the presence of oxygen to generate reactive oxygen species to clean fouled membranes' surface. The results showed that photo-cleaning was very effective to recover membrane flux.Öğe From peripherally unsubstituted subphthalocyanines with anti-inflammatory activity on macrophages to tri-iodo derivatives with adjuvant and immunostimulatory functions(World Sci Publ Co Inc, 2019) Ayaz, Furkan; Yuzer, Abdulcelil; Ince, MineIn this study we evaluated the impact of iodine substitution on the ability of subphthalocyanines (SubPc) to stimulate or regulate the function of macrophages. Previous studies have focused on the usage of phthalocyanines and their derivatives as treatment options against different types of cancer. In order to obtain better prognosis rates, their possible effects on the immune system cells should be delineated. Unique subphthalocyanines were designed and synthesized by our group and a derivative was generated via iodine substitution. In our study we further tested the effects of the new Subpcs on macrophage cell lines. Macrophages play an important role in the immune system through cytokine production and antigen presentation to other types of the immune system cells. They can define the type and the strength of the immune responses against a particular danger signal. Based on pro-inflammatory cytokine (TNF alpha, IL1 beta and 1L6) production levels by macrophages, unsubstituted SubPc had anti-inflammatory properties. However, iodine substitution on the same SubPc created a completely opposite effect since these iodo-substituted SubPc exerted an immunostimulatory effect on macrophages based on significant increases in the pro-inflammatory cytokine production levels compared to the untreated controls. While SubPcs can be used to suppress the pro-inflammatory activities of the macrophages, iodine-substituted SubPcs have potentials to be used as adjuvants and inununostimulatory molecules.Öğe From peripherally unsubstituted subphthalocyanines with anti-inflammatory activity on macrophages to tri-iodo derivatives with adjuvant and immunostimulatory functions -2(World Scientific Publishing Co. Pte Ltd, 2019) Ayaz, Furkan; Yuzer, Abdulcelil; Ince, MineConjugation of iodine to SubPcs gives them both immunostimulatory and immunomodulatory characteristics based on the changes in the pro-inflammatory cytokine secretion levels by macrophages. SubPcs with no iodine conjugation acted as anti-inflammatory agents and did not have immunostimulatory potential. © 2019 World Scientific Publishing Company.Öğe Imaging and detection of cell apoptosis by In vitro photodynamic therapy applications of zinc (II) phthalocyanine on human melanoma cancer(Elsevier, 2021) Zeinali, Sevda; Tuncel, Ayca; Yuzer, Abdulcelil; Yurt, FatmaThis study aims to investigate the photodynamic therapy (PDT) effects on MeWo (human melanoma cells) and HaCaT (normal human keratinocyte cells) by light stimulation of different concentrations of Zinc (II)-tetra-tertbutyl-phthalocyaninato (ZnPc). MTT viability assay data indicated that a 25 mu M concentration of ZnPc is cytotoxic to the melanoma cancer cells while this concentration of ZnPc is not cytotoxic for the HaCaT cell line. Moreover, the results showed that photoactivated ZnPc at 12.5 mu M concentration reduced the cell viability of the MeWo cell line to about 50 %. At this photosensitizing concentration, the efficacy of light doses of 20, 30, 40, and 50 J/cm(2) was evaluated against MeWo and HaCaT cells. ZnPc at a concentration of 12.5 mu M activated with a light dose of 50 J/cm(2) was the most efficient for the killing of MeWo cells. In conclusion, the 12.5 mu M of ZnPc with the treatment light dose of 50 J/cm(2) from a RED light source was adequate to destroy MeWo cells by the ROS-induced apoptosis mechanism. It also exhibited low killing effects on healthy HaCaT cells. These findings are supported by the results of apoptosis with the Annexin V & Dead Cell Kit and fluorescence imaging.Öğe Immunomodulatory activities of zinc(II)phthalocyanine on the mammalian macrophages through p38 pathway: Potential ex vivo immunomodulatory PDT reagents(Academic Press Inc Elsevier Science, 2019) Yuzer, Abdulcelil; Ayaz, Furkan; Ince, MineA series of zinc phthalocyanine having imidazolyl moieties was synthesized. These compounds' immunostimulatory and immunomodulatory activities were tested on the mammalian macrophages in vitro. In the absence of photo induction neither dmso soluble nor the water soluble imidazole Pc had any immunostimulatory or immunomodulatory effect on the macrophage activity based on the differences in the pro-inflammatory cytokine secretion levels compared to the control groups. Upon photo induction, especially, at 5 min exposure time both derivatives lead to an increased pro-inflammatory cytokine secretion level by LPS activated macrophages. Whereas, this effect was completely reversed after 10 min of light treatment and both derivatives gained stark anti-inflammatory potential. Our molecules were cell penetrating and exerted their effects by regulating the phosphorylation levels of p38. This study is one of its first examples suggesting differential immunomodulatory photo dynamic therapy applications of phthalocyanine derivatives depending on light exposure time as well as their possible route of modulating the intracellular signaling pathways.Öğe Non-canonical anti-cancer, anti-metastatic, anti-angiogenic and immunomodulatory PDT potentials of water soluble phthalocyanine derivatives with imidazole groups and their intracellular mechanism of action(Elsevier, 2022) Ayaz, Furkan; Yetkin, Derya; Yuzer, Abdulcelil; Demircioglu, Kubra; Ince, MineCancer is currently a leading health issue globally. Chemotherapy is a prominent treatment method but due to undesired side effects t, there has been a need for novel less toxic approaches. Photodynamic therapy may be listed among the alternatives for efficient and potentially less detrimental applications of cancer therapy. Canonical photodynamic therapy (PDT) approach requires a light source with a specific wavelength of light, a nontoxic photosensitizer and molecular oxygen. PDT creates the desired effect by the photochemical reaction created through interaction of these components to create reactive oxygen species that will act on the cancer cells to enable anti-cancer activities. In our study we focus on non-canonical PDT application. In this approach we are not only aiming to eliminate cancer cells in the environment but also test the anti-metastatic, anti-angiogenic and possible immunomodulatory activities of the novel photosensitizers. Moreover, in our approach, we studied the intracellular pathways that are crucial for carcinogenesis, cell cycle, apoptosis, angiogenesis, metastasis and immune function to decipher the mechanism of the action for each compound. Reactive oxygen species based explanation was not valid in our study, hence it brings out a non canonical approach to PDT applications. Our results suggests that Phthalocyanine derivatives with imidazole groups can be effectively used against lung, colon, breast and prostate cancer while differentially effecting metastasis, angiogenesis, cell cycle, apoptosis and immune system cell's activities. Based on the results, PDT application of these phthalocyanine derivatives can be an effective treatment option to replace chemotherapy to minimize the potential side effects.Öğe Photo induced anti-inflammatory activities of a Thiophene substituted subphthalocyanine derivative(Elsevier, 2020) Onal, Harika Topal; Yuzer, Abdulcelil; Ince, Mine; Ayaz, FurkanMaterials that possess photo induced biological activities present opportunities for more localized, targeted and efficient treatment options that may also reduce side effects. There have been studies supporting photo induced effects of photosensitizers as anti-cancer, anti-inflammatory and anti-microbial agents. In this study, we tested photo activated anti-inflammatory effects of a Thiophene substituted subphthalocyanine (SubPc) derivative. Thiophene and its derivatives are well known for their anti-inflammatory and anti-microbial effects. There are unwanted side effects associated with Thiophene derivatives. By substituting this biologically active molecule to SubPc structure we acquired control over its activation. Upon light treatment this derivative exerted anti-inflammatory activity on the mammalian macrophages in vitro based on the substantial decrease in extracellular inflammatory cytokine levels. Our results suggest that Thiophene substituted SubPc derivative has photo induced anti-inflammatory activities. This material can be used for the treatment of patients suffering from chronic inflammation that are not associated with a bacterial burden such as autoimmune diseases and inflammatory or allergic reactions.