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    Anti-Cancer and Anti-Inflammatory Activities of Bromo- and Cyano-Substituted Azulene Derivatives
    (Springer/Plenum Publishers, 2020) Ayaz, Furkan; Yuzer, Abdulcelil; Ince, Tuncay; Ince, Mine
    Natural 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.
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    Antiinflammatory photodynamic therapy potential of polyoxyethylene-substituted perylene diimide, nitrocatechol, and azo dye
    (Tubitak Scientific & Technological Research Council Turkey, 2021) Hakli, Ozgul; Ocakoglu, Kasim; Ayaz, Furkan
    Photodynamic therapy (PDT) applications enable light-controlled activation of drug candidates instead of their constitutive activities to prevent undesired side effects associated with their constant activities. A specific wavelength of light is utilized to enable electron mobility in the chemical structure, which results in differential activities that may alter cell viability and cellular functions. Canonical photodynamic therapy applications mostly focus on cytotoxicity-based antimicrobial and anticancer properties of the PDT agents. In this study, we focused on subtoxic concentrations of three different molecules containing polyoxyethylene group and examined their antiinflammatory activities on stimulated mammalian macrophages. Stimulated macrophages produce proinflammatory cytokines TNF and IL6. In the presence of a light source, our PDT agents were activated for 5 and 10 min during their application to the macrophages. Based on the ELISA results, the compounds had anti-inflammatory PDT activities. Trypan blue staining results suggest that these derivatives exerted their activities without leading to cytotoxicity. Our results suggest noncanonical PDT applications of these derivatives that can alter cellular activities without leading to cell death.
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    Beyond the Conventional Photodynamic Therapy by Water-Soluble Phthalocyanines
    (Wiley-V C H Verlag Gmbh, 2022) Yuzer, Lecturer Abdulcelil; Demircioglu, Perihan Kubra; Yetkin, Lecturer Derya; Ince, Mine; Ayaz, Furkan
    Compared to the classical chemotherapy applications, PDT applications are based on a non-toxic compound that can be specifically activated by shining a certain wavelength of light. Constitituvely active chemotherapy drug agents lead to detrimental and unwanted side effects that halt the normal life standards of the cancer patients. Localized and controlled activation of the drug agents by PDT applications aims to overcome the side effects associated with the treatment. In our study we synthesized a unique set of phthalocyanine molecules that are water soluble to make them biocompatible. Moreover, these compounds anti-cancer activities were measured from multiple angles. Anti-cancer PDT activities of the derivatives were studied by testing their effects on the cell proliferation, apoptosis and cell cycle progression. Moreover, these derivatives anti-metastatic, anti-angiogenic and immunomodulatory photodynamic activities were comprehensively studied by focusing on the intracellular signaling pathways that may play important roles in carcinogenesis, angiogenesis, metastasis and immune reactions. For the first time to our knowledge we are presenting data beyond the classical or canonical PDT applications in which generation of the reactive oxygen species (ROS) is explained as the main mechanism of the action for the PDT applications. Our results suggest that non-canonical PDT activity can be observed independent of the ROS generation efficiencies probably by affecting the intracellular signaling pathways. These novel set of phthalocyanine derivatives may find applications against colon, lung, breast and prostate cancer.
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    Differential effects of aminochlorin derivatives on the phagocytic and inflammatory potentials of mammalian macrophages
    (Elsevier, 2020) Ayaz, Furkan; Ocakoglu, Kasim
    Chlorin derivatives have been known for their biological activities. Especially due to their advanced electron transfer capacity they have been used as photodynamic therapy agent both a clinical and laboratory scales. Photodynamic therapy (PDT) against cancer or an infectious disease aims the development of less side effect on the patient since the activation of the inert drug molecule will start only after the light treatment. In order to increase our library of photodynamic therapy agents, we generated a set of chlorin derivatives and tested their PDT potential on the immune system cells; macrophages. Macrophages are known for their primary role as an inflammatory cell type that have been found in the inflamed tissues of the patients with autoimmune and inflammatory disorders as well as in the tumor environment as tumor associated macrophages. Our derivatives had anti-inflammatory PDT potential in the presence of a danger mimic but they lacked immunostimulatory effect. Moreover, these cells' ability to eliminate an infectious agent or present the danger molecules to the other immune cells were tested by phagocytosis assay in the presence of our compounds. Chlorin derivatives were able to differentially regulate the phagocytic activity of the mammalian macrophages.
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    Differential Immunomodulatory Activities of Schiff Base Complexes Depending on their Metal Conjugation
    (Springer/Plenum Publishers, 2019) Ayaz, Furkan; Gonul, Ilyas; Demirbag, Burcu; Ocakoglu, Kasim
    Immunomodulatory compounds have become crucial with advances in immunotherapy. Using our own immune system cells, we can direct the immune cell function and develop desired response against a certain threat. Immunotherapy applications have been suggested against tumors, autoimmune disorders, and infectious diseases. Vaccination can be considered as one of the best known example of immunotherapy. Infectious agent's signature molecular structures are introduced to the immune cells together with the adjuvants that further activate the immune cells to mount a proper immune response and memory. Immunotherapy and vaccine formulations are in constant need of a library of immunomodulatory reagents that can be applied depending on the target. In order to expand the number of immunomodulatory reagents that can find medicinal applications, our group has been testing unique chemical structures on the immune system cells, especially macrophages. Schiff base complexes are known for their anti-inflammatory and antimicrobial activities. In this study, we used previously characterized Schiff base complexes with different metal conjugations. These molecules had differential immunostimulatory and immunomodulatory potentials on macrophages in vitro depending on the type of the conjugated metal. After light exposure, these complexes changed their characteristics and became powerful anti-inflammatory complexes. Due to their possible antimicrobial potentials, we also tested their activities against gram negative and gram positive bacteria. All of the complexes exerted antimicrobial activities which were not light responsive. Here, we present Schiff base complexes with differential immunostimulatory and immunomodulatory activities that can also efficiently eliminate gram positive and gram negative bacteria. Upon photo activation, they block the production of inflammatory TNF alpha cytokine. Therefore, together with the light, they can be used to treat bacterial infections associated with damaging inflammation.
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    Electrospun nanofiber mats caged the mammalian macrophages on their surfaces and prevented their inflammatory responses independent of the fiber diameter
    (Nature Portfolio, 2024) Ayaz, Furkan; Demir, Didem; Bölgen, Nimet
    Poly-?-caprolactone (PCL) has been widely used as biocompatible materials in tissue engineering. They have been used in mammalian cell proliferation to polarization and differentiation. Their modified versions had regulatory activities on mammalian macrophages in vitro. There are also studies suggesting different nanofiber diameters might alter the biological activities of these materials. Based on these cues, we examined the inflammatory activities and adherence properties of mammalian macrophages on electrospun PCL nanofibrous scaffolds formed with PCL having different nanofiber diameters. Our results suggest that macrophages could easily attach and get dispersed on the scaffolds. Macrophages lost their inflammatory cytokine TNF and IL6 production capacity in the presence of LPS when they were incubated on nanofibers. These effects were independent of the mean fiber diameters. Overall, the scaffolds have potential to be used as biocompatible materials to suppress excessive inflammatory reactions during tissue and organ transplantation by caging and suppressing the inflammatory cells.
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    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, Mine
    In 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.
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    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, Mine
    Conjugation 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.
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    Immunoactive photosensitizers had photodynamic immunostimulatory and immunomodulatory effects on mammalian macrophages
    (Elsevier, 2020) Ayaz, Furkan; Demirbag, Burcu; Ocakoglu, Kasim
    Photodynamic compounds have great potential in biological applications. Their controlled and localized activation with specific wavelength of light provides opportunities to potentially evade the side effects of today's cancer therapies. Biologically compatible photosensitizers can be used in therapy against cancer, infections as well as inflammatory and immune disorders. In this study, we examined chlorophyll derivatives for antimicrobial, immunostimulatory and immunomodulatory activities. Under dark conditions, these chlorophyll derivatives had strong anti-microbial activities on gram positive S.aureus and gram negative E.coli. Photo activation of the chlorophyll derivatives did not alter their anti-microbial activities on gram negative or gram positive bacteria. In order to examine how these anti-microbial chlorophyll derivatives might effect immune reaction of macrophages, they were tested on mammalian macrophages. They had immunostimulatory activities on them in the dark conditions since they led to increased TNF and IL6 cytokine production even in the absence of stimulants lipopolysaccharide (LPS) and lipoteichoic acid (LTA). Photo-activation of the compounds led to decrease in pro-inflammatory cytokines, TNF and IL6, production by LPS or LTA activated macrophages. Therefore, these molecules can be used to regulate the immune response in the patients with bacterial infection while leading to death of bacteria. Light induced activation of the compounds could enable localized and controlled activation of their anti-inflammatory effects.
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    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, Mine
    A 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.
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    Investigating the Immunostimulatory and Immunomodulatory Effects of cis and trans Isomers of Ruthenium Polypyridyl Complexes on the Mammalian Macrophage-Like Cells
    (Wiley-V C H Verlag Gmbh, 2020) Ayaz, Furkan; Colak, Suleyman Gokhan; Ocakoglu, Kasim
    Immunomodulatory and immunostimulatory compounds are drug candidates for the regulation of the function of immune system cells to fight against disease conditions including cancer to autoimmunity as well as inflammatory disorders. Due to the electron transfer capacity of photosensitizers in solar cell structures, we hypothesized that they can also be used to regulate the immune system cells' functions possibly through interfering with their electron transfer related activities. We examined thecisandtransisomers (cis-Ru andtrans-Ru) of ruthenium polypyridyl complex on the activated macrophage-like cellsin vitro. Our results suggest immunostimulatory and positive immunomodulatory roles for the ruthenium complex.These compounds increased the production of tumor necrosis factor (TNF) pro-inflammatory cytokine by macrophage-like cells. Therefore, bothcisandtransisomers can be used as a new generation of adjuvant candidates in the vaccine formulations to further boost the activity of immune cells against the disease agent or antigen.
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    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, Mine
    Cancer 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.
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    Novel Copper Bearing Schiff Bases with Photodynamic Anti-Inflammatory and Anti-Microbial Activities
    (Springer, 2020) Ayaz, Furkan; Gonul, Ilyas; Demirbag, Burcu; Ocakoglu, Kasim
    Schiff bases and their copper complexes have been previously studied for their anti-inflammatory, anti-tumor as well as anti-microbial activities. Schiff bases can be derivatized to gain photoluminiscence capacity. This property of the schiff bases enables the transfer of the electrons upon absorption of the light at a specific wavelength. In this study, we exploited this attribute of novel copper bearing schiff bases and tested their photodynamic biological activities. These compounds exerted photodynamic anti-inflammatory activities on the in vitro activated mammalian macrophages. Compared with salicylic acid control groups, these novel schiff bases had stronger activity which became more prominent with photo-induction. Moreover, they also had anti-microbial activity on gram negative bacteria E.coli and gram positive bacteria S.aureus.This anti-microbial activity was stronger than that of Neomycin on both bacterial strains. Our results suggest their potential use as anti-inflammatory and anti-microbial agents both in the dark as well as after photo-induction.
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    Photo induced anti-inflammatory activities of a Thiophene substituted subphthalocyanine derivative
    (Elsevier, 2020) Onal, Harika Topal; Yuzer, Abdulcelil; Ince, Mine; Ayaz, Furkan
    Materials 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.
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    Photo-induced anti-inflammatory activities of chloro substituted subphthalocyanines on the mammalian macrophage in vitro
    (Elsevier Science Bv, 2019) Ayaz, Furkan; Ugur, Naz; Ocakoglu, Kasim; Ince, Mine
    In this study, a series of subphthalocyanines (SubPcs) derivatives were synthesized to generate unique immunomodulatory molecules that can be activated through photo-induction. Immunomodulatory agents have a great potential in medicine to manipulate the immune system according to our needs and prevent disease symptoms. Inflammation is one of these symptoms and macrophages play a crucial role in the generation of inflammatory responses. Being able to control the activity of these agents through photo-induction enables the fine tuning on their activities in a location specific and non-invasive manner with possibly minor side effects. Mammalian macrophages' pro-inflammatory activity was examined in the presence of our compounds as well as LPS as a danger mimic. These compounds exerted photo-induced anti-inflammatory activities on the macrophages. Number of Cl atoms was a defining factor in their photo-induced anti-inflammatory immunomodulatory efficiencies.
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    Photodynamic Anti-Inflammatory Activity of Porphyrin Derivative on In-Vitro Activated Macrophages
    (Springer, 2023) Hakli, Ozgul; Ocakoglu, Kasim; Ayaz, Furkan
    Porphyrin derivatives have been known for their photodynamic therapy (PDT) application potential. In the present work, we have studied an asymmetric tetraphenyl substituted porphyrin derivative synthesized previously. Although traditional PDT applications focus on antibacterial and anti-cancer activities of the drug candidates, these compounds may have functional properties at subtoxic concentrations due to the chemically active groups that they carry. In this study, we aimed to investigate the anti-inflammatory PDT potential of this porphyrin derivative. For this purpose, mammalian macrophage cells were used. Trypan blue staining was done to confirm that this compound was effective at non-toxic concentrations. Moreover, TNF and IL6 ELISAs were done to the supernatants of the stimulated cells. Xenon light exposure was done to activate the porphyrin derivative. Our results suggest that this derivative had differential effects on these cytokine production levels by activated macrophages. These effects are light activation-dependent which makes this derivative a viable option for anti-inflammatory PDT applications. Moreover, it did not exert any cytotoxic effect at concentration used both in the dark and under light conditions.
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    Unique photodynamic antimicrobial Schiff bases and their copper complexes exert immunomodulatory activity on mammalian macrophages
    (Taylor & Francis Ltd, 2020) Gonul, Ilyas; Demirbag, Burcu; Ocakoglu, Kasim; Ayaz, Furkan
    Antibiotic resistance has been a growing problem for the public health. Especially the hospitalized patients are at high risk due to emergence of superbugs that can evade a wide range of antibiotics in use. In order to circumvent this major problem, new candidates of antimicrobial agents should be created and tested for their efficacies. Moreover, having antimicrobial agents that could get activated with light exposure (antimicrobial PDT) would create a great advantage in terms of decreasing the required effective dose as well as controlled localized activation of the candidate drugs. Schiff base derivatives have antimicrobial, antitumor, and anti-inflammatory activities. In this study, we used a unique set of Schiff base derivatives with and without copper for antimicrobial PDT applications both on gram-negative Escherichia coli and gram-positive Staphylococcus aureus. Our compounds had strong antimicrobial PDT potential especially with the addition of copper into their structures. Moreover, these Schiff base derivatives' possible immunomodulatory activities were tested on mammalian macrophages in vitro. These compounds had photodynamic anti-inflammatory activities as well. Our results suggest that these unique Schiff bases can be utilized in antimicrobial PDT applications that can also alter the function of the immune system cells to suppress excessive inflammation.
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    Water-Based Synthesis of Copper Chalcogenide Structures and Their Photodynamic Immunomodulatory Activities on Mammalian Macrophages
    (Springer, 2022) Ayaz, Furkan; Colak, Suleyman Gokhan; Ocakoglu, Kasim
    Generation of novel and versatile immunomodulatory agents that could suppress excessive inflammation has been crucial to fight against chronic inflammatory and autoimmune disorders. Immunomodulatory agents regulate the function of immune system cells to manage their activities. Current therapy regimens for the inflammatory and autoimmune disorders rely on immunomodulatory drug molecules but they are also associated with unwanted and severe side effects. In order to prevent the side effects associated with drug molecules, the field should generate novel immunomodulatory drug candidates and further test them. Moreover, the generation of photodynamic immunomodulatory molecules would also decrease possible side effects. Photodynamic activation enables specific and localized activation of the active ingredients upon exposure to a certain wavelength of light. In our study, we generated copper-based chalcogenide structures in gel and nanoparticle form by using a water-based method so that they are more biocompatible.After their chemical characterization, they were tested on mammalian macrophages in vitro. Our results suggest that these molecules were anti-inflammatory in dark conditions and their anti-inflammatory potentials significantly increased upon xenon light treatment. We are presenting novel photodynamic immunomodulatory agents that can be used to suppress excessive inflammation in disease conditions that have been associated with excessive inflammation.
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    Yeni Fftalosiyanin Türevlerinin Sentezi ve Anti-Kanser, Anti-Anjiyojenik, Anti-Metastatik ve İmmünomodülatör Uygulamaları
    (2022) Ayaz, Furkan; Ince, Mine
    Kanser dünyadaki sağlık sorunlarının başında gelmektedir ve birçok farklı türü olan kanserin tedavisi henüz tam olarak bulunamamış olmakla birlikte hızla yayılmaktadır. Yıllardır kullanılan ve kabul görmüş cerrahi, kemoterapi ve radyoterapi gibi tedavi yöntemleri ise oldukça fazla yan etkiye sahiptir ve hastaların yaşam kalitesini ciddi şekilde düşürmektedir. Birçok alternatif tedavi yöntemi içerisinde en az yan etkiye sahip, en etkili ve gelecek vaat eden yöntem ise Fotodinamik Terapi (PDT)?dir. Fotodinamik etkinin oluşabilmesi için üç temel bileşen vardır; ışığa duyarlı ve toksik olmayan bir fotosensör, uygun dalgaboyunda ışık ve moleküler oksijen. PDT prensipte bu üç bileşenin bir seri fotokimyasal mekanizma ile tümörlü dokuda meydana getirdiği etkiye dayanmaktadır. Etkili bir fotodinamik terapi uygulaması için, ışığın fotosensör tarafında absorblanması ve enerjinin moleküler oksijene en kısa sürede transfer edebilmesi gerekmektedir. Şu durumda, uygun fotosensitörlerin tasarımı ve sentezi PDT etkinliği için kilit faktördür. Bugüne kadar yeni bir çok aromatik fotosensör sentezlenip PDT aktiviteleri farklı kanser hücrelerinde test edilmiştir. Kanser hücrelerinin yok edilmesi üzerine dikkate değer başarılar kazanılmakla beraber bu çalışmaların çoğu kanseri bir bütün olarak ele almaktan ziyade sadece kanser hücrelerinin yok edilmesi üzerine yoğunlaşmaktadır. Bu durum kanser hücrelerinin yayılmasını ve hastanın bağışıklık sistemini zayıflatarak hastalığın tekrar etmesini önleyememektedir. Bu yüzden kansere karşı mücadele kanserli hücreleri öldürmenin yanı sıra; farklı dokulara göç etme yetisini, damar oluşumunu engelleyip göç yollarına kapatma etkinligini ve de bağışıklık sistemi hücrelerini doğru şekilde yönlendirip tümör hücrelerine karşı topyekin bir tepki oluşturma kabileyini hedeflemelidir ki başarıya ulaşabilsin. Ftalosiyanin ve porfirinler sahip oldukları fotofiziksel ve kimyasal özelliklerden dolayı biyolojik uygulamalarda en fazla kullanılan aromatik bileşiklerdir. Bugüne kadar bir çok ftalosiyanin türevinin kanser tedavisinde kullanımak üzere fotosensör ve ilaç aday potansiyelleri inclenmiş olmasına rağmen, bu fotosensörlerin kanser hücrelerini yok etme etkilerinin dışında konvansiyonel olmayan PDT ile bu türevlerin bağışıklık sistemine ve damar oluşumuna etkisi aynı anda incelenmemiştir. Bütün bu bilgilerin ışığında, mevcut proje önerisinde, kanser tedavisinde kullanılacak farklı metaller içeren suda çözünen yeni ftalosiyanin türevleri sentezlenecek ve biyolojik aktiviteleri akciğer, kolon, meme ve prostat kanser türleri üzerinde incelenecektir. Ftalosiyaninlerin kimyasal çeşitliliğe uygun olan moleküler yapıları, bu bileşiklerin biyolojik uygulamalar başta olmak üzere bir çok uygulama alanında amaca yönelik tasarlanmısını sağlamaktadır. İmidazol ve türevlerinin anti-kanser, anti-inflammatuvar, anti-tübreküloz, anti-viral, anti-parazitik, anti-mikrobiyal, anti-depresan ve analjezik etkilerinin olduğu bilinmektedir. Mevcut proje önresinde Pc lerin biyolojik aktivitelerini arttımak için imidazole türevlerinin periferal konuma bağlı olduğu yeni ftalosiyanin türevleri sentezlenecektir. Fotodinamik terapi uygulamalarında kanser hücrelerine karşı anti-proliferatif, apoptotik ve anti-metastatik etkilerinin yanı sıra anti-anjiyojenik ve bağışıklık sistemini düzenleyici etkileri de incelenecek olan yeni ftalosiyanin türevlerinin olası ilaç adayı olarak literatüre ve endüstriye sunulması hedeflenmektedir.