Antikanser potansiyele sahip bazı glukuronid türevi maddelerin sentezi ve radyoiodinasyon şartlarının incelenmesi
Küçük Resim Yok
Tarih
1996
Yazarlar
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Ege Üniversitesi
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
ÖZET Bu çalışmada, fenil-N-glukuronid, P-naftil-N-glukuronid, p-amino- fenil-N-glukuronid, p-fenilen-N-N'-diglukuronid gibi bazı N-glukuronid türevi maddeler sentez edilmiş ve radyoaktif iyod-131 ile işaretlenmiştir. Bu çalışmanın amacı, bazı toksik maddelerin yapısal toksisiteleri ile iyod-125 radyoaktif çekirdeğinin radyotoksisitesinin birleştirilebileceği anti-kanser maddeler üretebilmektir* Bilindiği gibi, bazı kanser hücrelerinde yüksek düzeyde P-glukuronid enzimi vardır. Bu enzim sayesinde glukuronid türevi bileşikler deglukuronidasyona uğrayarak bunların aglikon denen toksik kısımları seçimli olarak bu tür kanser hücreleri içine girerler. Ancak, bu tür bileşiklerin toksisiteleri anti-kanser ilaç olarak kullanımda pek etkili olamamaktadır. Öte yandan, Auger elektronları salıcısı olarak bilinen iyod-125'in büyük bir radyotoksik etkisinin olduğu bilinmektedir. Bu sebeblerden dolayı, iyod-125'in radyotoksisitesi ile toksik maddelerin yapısal toksisitelerinin birleştirilip, seçimli olarak kanserli hücrelere gönderilebilmesi kanser araştırmalarında büyük önem taşımaktadır. Bu çalışmada elde edilen sonuçlar, N-glukuronid türevi bileşiklerin radyoaktif iyod-131 ile işaretlenmesi için uygulanan iodogen methodunun, radyoaktif iyod-125 ile işareleme için de aynen geçerli olduğunu göstermiştir. Sonuç olarak, iyod-125 veya iyod-131 ile işaretli olan bu glukuronid türevi maddelerin gerek teşhis gerekse tedavi amacıyla kanser araştırmalarında kullanılabilmesi mümkündür. 53
SUMMARY in this stucly some N-glucuronide conjugates such as phenyl-N- glucuronide, p-naphthyl-N-glucuronide, p-amino-phenyl-N-glucuronide and p-phenylene-N-N'-diglucuronide were synthesized and radiolabelled with 13!I. The principal aim of this study was producing some anti-cancer prodrugs which are able to combine simultanouesly the extreme radiotoxicity of 125I radionuclide with the cytotoxicity of some toxic agents. it is well known that some kind of cancer cells have high level of p-glucuronidase activity. This enzyme is able to deglucuronidate ali kind of glucuronide conjugates. The aglycone portions of these glucuronide conjugates can be selectively incorporated into this kind of cancer cells because of this enzyme activity. Nevertheless, their cytotoxicities are not sufficiently enough for their using as being effective anti-cancer drugs. t-je On the other hand, it is also well known that I radionuclide as a specific Auger electrons emitter has extreme radiototoxicity effects on the living systems. For this reason, the combination of the radiotoxicity of !25I with the cytotoxicity of some toxic agents, and their selectively incorporation into the cancer cells has a large potential application in cancer research. The results obtained in this study showed that the iodogen method applied for the radioiodination of N-glucuronide conjugates using 131I radionuclide can similarly be applied for the radioiodination of the same N-glucuronide conjugates with 125I radionuclide, too, and consequently 51131 12*5 these radioiodinated agents either with I or "I will be able to be used in as diognaslig and therapeutic agents in cancer research studies. 52
SUMMARY in this stucly some N-glucuronide conjugates such as phenyl-N- glucuronide, p-naphthyl-N-glucuronide, p-amino-phenyl-N-glucuronide and p-phenylene-N-N'-diglucuronide were synthesized and radiolabelled with 13!I. The principal aim of this study was producing some anti-cancer prodrugs which are able to combine simultanouesly the extreme radiotoxicity of 125I radionuclide with the cytotoxicity of some toxic agents. it is well known that some kind of cancer cells have high level of p-glucuronidase activity. This enzyme is able to deglucuronidate ali kind of glucuronide conjugates. The aglycone portions of these glucuronide conjugates can be selectively incorporated into this kind of cancer cells because of this enzyme activity. Nevertheless, their cytotoxicities are not sufficiently enough for their using as being effective anti-cancer drugs. t-je On the other hand, it is also well known that I radionuclide as a specific Auger electrons emitter has extreme radiototoxicity effects on the living systems. For this reason, the combination of the radiotoxicity of !25I with the cytotoxicity of some toxic agents, and their selectively incorporation into the cancer cells has a large potential application in cancer research. The results obtained in this study showed that the iodogen method applied for the radioiodination of N-glucuronide conjugates using 131I radionuclide can similarly be applied for the radioiodination of the same N-glucuronide conjugates with 125I radionuclide, too, and consequently 51131 12*5 these radioiodinated agents either with I or "I will be able to be used in as diognaslig and therapeutic agents in cancer research studies. 52
Açıklama
Bu tezin, veri tabanı üzerinden yayınlanma izni bulunmamaktadır. Yayınlanma izni olmayan tezlerin basılı kopyalarına Üniversite kütüphaneniz aracılığıyla (TÜBESS üzerinden) erişebilirsiniz.
Anahtar Kelimeler
Kimya, Chemistry, Enzimler, Enzymes, Glukuronid, Glucuronide, Kanser hücreleri, Cancer cells
