Enzymatic synthesis of (125/131)I labeled 8-hydroxyquinoline glucuronide and in vitro/in vivo evaluation of biological influence.
8-Hydroxyquinoline (8-OHQ) is a long-known molecule which due to its metal-complexation ability is frequently used for analysis. It is also called oxine. Oxine and derivatives have been investigated to process antitumor and antimicrobial activities. 8-Hydroxyquinolyl-glucuronide (8-OHQ-Glu) was enzymatically synthesized using microsome preparates separated from Hutu-80 cells, labeled with (125)I to perform a radionuclide labeled prodrug and investigated of its biological affinities on Hutu-80 (human duodenum intestinal adenocarcinoma), Caco-2 (human colorectal adenocarcinoma), Detroit 562 (human pharynx adenocarcinoma) cells and ACBRI 519 (primary human small intestine epithelial cells) in this work. UDP-glucuronyl transferase (UDPGT) rich microsome preparates, which are used for glucuronidation in enzymatic synthesis, were extracted from Hutu-80 cells. 8-OHQ-Glu components were labeled using iodogen method with (125)I and (131)I. Structural analyses were performed with LC/MS/MS, (1)H NMR and (13)C-MMR for identify and measure chemical constituents. Results confirmed expected molecular structure. 8-OHQ-Glu could successfully radioiodinated with (125/131)I according to iodogen method. (125)I-8-OHQ-glucuronide incorporated with human gastrointestinal cancer cells such as Detroit-562 (human pharynx adenocarcinoma) (12.6%), Caco-2 (human colorectal adenocarcinoma) (7.8%), Hutu- 80 (human duodenum intestinal adenocarcinoma) (9.5%) and ACBRI 519 (primary human small intestine epithelial cells) (6.40%). (131)I-8-OHQ-Glu was tested in mice bearing subcutaneously implanted Caco-2 colorectal adenocarcinoma cells. The results demonstrated that radioiodinated 8-OHQ-Glu may be promising anticancer prodrug.
Ege University, Institute of Nuclear Science, 35100 Bornova, Izmir, Turkey.
Reyhan
R
Yeşilağaç
Perihan
P
Ünak
E İlker
Eİ
Medine
Çiğdem A
ÇA
İçhedef
Turkan
T
Ertay
F Z Biber
FZ
Müftüler
D000818:Animals; D018938:Caco-2 Cells; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D006912:Hydroxyquinolines / Q000378:metabolism*; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D015125:Oxyquinoline / Q000493:pharmacokinetics; D011355:Prodrugs
D006912:Hydroxyquinolines; D007457:Iodine Radioisotopes; D011355:Prodrugs; C056147:8-hydroxyquinoline glucuronide; D015125:Oxyquinoline