Computational and biological evaluation of quinazolinone prodrug for targeting pancreatic cancer.

摘要: Our concept of enzyme-mediated cancer imaging and therapy aims to use radiolabeled compounds target hydrolases over-expressed on the extracellular surface solid tumors. A data mining approach identified sulfatase 1 (SULF1) as an enzyme expressed pancreatic cells. We designed, synthesized, characterized 2-(2′-sulfooxyphenyl)-6-iodo-4-(3H)-quinazolinone (IQ2-S) well its radioiodinated form (125IQ2-S) a prodrug with potential for hydrolysis by SULF1. IQ2-S was successfully docked in silico into three enzymes – homolog SULF1, alkaline phosphatase, prostatic acid phosphatase. The incubation 125IQ2-S 125IQ2-P solution confirms docking results selectivity analogs. both radioactive produces water-insoluble, fluorescent product 2-(2′-hydroxyphenyl)-6-[125I]iodo-4-(3H)-quinazolinone (125IQ2-OH). vitro 127IQ2-S 127IQ2-P pancreatic, ovarian, prostate cells expressing studied also their precipitation 127IQ2-OH crystals cell surface. To our knowledge, these findings are first report targeting substrate SULF1 that this may be potentially useful (123I/124I/131I) radiotherapy (131I) cancer.