Publication: Fotodinamik terapi amaçlı piperidin sübstitüe yeni indiyum ftalosiyaninlerin sentezi, karakterizasyonu, fotofiziksel ve fotokimyasal özelliklerinin incelenmesi
Abstract
Kanser, çağımızın ölüm oranı en yüksek hastalıklarından biridir. Kanser hastalığının tedavisi için uzun yıllar boyunca farklı yaklaşımlar kullanılmış ancak kesin bir başarı sağlama konusunda maalesef yetersiz kalınmıştır. Günümüzde, süre gelen tedavi yöntemleri devam ederken diğer taraftan alternatif, uygulanabilir ve olumlu sonuçlar elde edilebilecek yeni yöntemler geliştirilmeye devam edilmektedir. Bu yaklaşımlardan biri de Fotodinamik Terapi (PDT) yaklaşımıdır. PDT uygulaması üç temel bileşene dayanmaktadır. Işık, oksijen ve spesifik dalga boylarında aktive olabilen fotosensitizer adı verilen maddenin etkileşimleri sonucu singlet oksijen üretimi gerçekleşmekte ve bunun sonucunda hücre ölümleri gerçekleşmektedir. Ftalosiyanin bileşikleri PDT uygulamalarında kullanılabilecek uygun fotosensitizerler olarak öne çıkmaktadır. Ftalosiyaninler, konjuge 18-π elektron yapısına sahip, makrohalkalı, aromatik bileşiklerdir. Özellikle yüksek dalga boyunda (yaklaşık 700nm) ışığı absorblayabilme kapasiteleri PDT uygulamaları için oldukça etkin olabileceklerini göstermektedir. Işıksız ortamda ftalosiyaninlerin herhangi bir toksik etkinlik göstermemeleri ve singlet oksijen verimlerinin yüksek olması da PDT uygulamaları tercih edilebilirliğini artırmaktadır. Bu tez çalışmasında 2,6-disübstitüe fenol grubu içeren piperidin sübstitüe özgün ftalonitril türevi bileşikler sentezlenmiş ve bu bileşiklerden, indiyum iyodür metal tuzu kullanılarak yeni tip indiyum(III) ftalosiyanin fotosensitizer bileşiklerinin sentezi gerçekleştirilmiştir. Sentezi hedeflenen bileşiklerin yapı ve karakterizasyon çalışmaları FT-IR, 1H-NMR, 13C-NMR, UV-Vis ve kütle spektroskopisi ile aydınlatılmıştır. Sentezi gerçekleştirilen ftalosiyaninlerin fotofiziksel ve fotokimyasal özellikleri incelenmiş fotodinamik terapi uygulamalarında kullanılabilirliği araştırılmıştır. Ayrıca, sentezlenen fotosensitizer bileşiklerin in-vitro hücre çalışmaları da yapılarak çeşitli kanser hücrelerinde davranışları ve etkinlikleri gözlemlenmiş, ilaç etki potansiyeli ve sağlık çalışmaları için uygunlukları değerlendirilmiştir.
Cancer is one of the diseases of our age with the highest mortality rate. Different approaches have been used for the treatment of cancer for many years, but unfortunately, they have been insufficient to achieve a definite success. Today, while ongoing treatment methods continue, on the other hand, alternative, applicable and new methods that can achieve positive results continue to be developed. One of these approaches is Photodynamic Therapy (PDT). PDT application is based on three basic components. As a result of the interaction of light, oxygen and a substance called photosensitizer which can be activated at specific wavelengths, singlet oxygen production occurs and it causes to cell deaths. Phthalocyanine compounds stand out as suitable photosensitizers that can be used in PDT applications. Phthalocyanines are macrocyclic, aromatic compounds with conjugated 18-π electron structure. Their capacity of absorbing light, especially at high wavelengths (approximately 700nm), indicates that they can be highly effective for PDT applications. The fact that phthalocyanines do not show any toxic activity in the absence of light and their high singlet oxygen yields also increase preferability of phthalocyanines for PDT applications. In this thesis, piperidine substituted original phthalonitrile derivatives that containing 2,6-disubstituted phenol group were synthesized and new types of indium(III) phthalocyanine photosensitizer compounds were synthesized from these phthalonitrile compounds using indium(III) iodide metal salt. The structure and characterization studies of the synthesized compounds were elucidated by FT-IR, 1H-NMR, 13C-NMR, UV-Vis and mass spectroscopy. The photophysical and photochemical properties and usability in photodynamic therapy applications were investigated for synthesized phthalocyanine compounds. In addition, in-vitro cell studies of the synthesized photosensitizer compounds were carried out and their behavior and activity in various cancer cells were observed. The drug efficacy potential and their suitability for health studies were evaluated.
Cancer is one of the diseases of our age with the highest mortality rate. Different approaches have been used for the treatment of cancer for many years, but unfortunately, they have been insufficient to achieve a definite success. Today, while ongoing treatment methods continue, on the other hand, alternative, applicable and new methods that can achieve positive results continue to be developed. One of these approaches is Photodynamic Therapy (PDT). PDT application is based on three basic components. As a result of the interaction of light, oxygen and a substance called photosensitizer which can be activated at specific wavelengths, singlet oxygen production occurs and it causes to cell deaths. Phthalocyanine compounds stand out as suitable photosensitizers that can be used in PDT applications. Phthalocyanines are macrocyclic, aromatic compounds with conjugated 18-π electron structure. Their capacity of absorbing light, especially at high wavelengths (approximately 700nm), indicates that they can be highly effective for PDT applications. The fact that phthalocyanines do not show any toxic activity in the absence of light and their high singlet oxygen yields also increase preferability of phthalocyanines for PDT applications. In this thesis, piperidine substituted original phthalonitrile derivatives that containing 2,6-disubstituted phenol group were synthesized and new types of indium(III) phthalocyanine photosensitizer compounds were synthesized from these phthalonitrile compounds using indium(III) iodide metal salt. The structure and characterization studies of the synthesized compounds were elucidated by FT-IR, 1H-NMR, 13C-NMR, UV-Vis and mass spectroscopy. The photophysical and photochemical properties and usability in photodynamic therapy applications were investigated for synthesized phthalocyanine compounds. In addition, in-vitro cell studies of the synthesized photosensitizer compounds were carried out and their behavior and activity in various cancer cells were observed. The drug efficacy potential and their suitability for health studies were evaluated.