Medicinal Chemistry

We are interested both radio and chemotherapeutic agents, and we have a special interest in Boron Neutron Capture Therapy (BNCT), which is referred to the radiation generated from the capture reaction of thermal or epithermal neutrons by 10Boron isotopes. We have previously shown that, using conjugation of boron and targeting moieties to polymers we could achieve a 6-fold increase in the delivery of boron to colon-cancer tissues compared to the normal adjacent tissues.

Polymeric devices

We study the use of conjugated copolymers to increase the specificity of chemo and radiotherapy. In this approach, we use synthetic polymers which will have conjugated therapeutic molecules with high anti-tumor activity but have also side effects on other healthy tissues. At the same time the polymer are conjugated to targeting moieties that bind preferentially to cancer cells. The targeting moieties specifically brings the polymer-drug conjugate to the tumor cells rather than normal tissue, and increase the effectively of the treatment and reduce side effects in other organs.

Small Molecule synthesis

To improve tumor selectivity, we envisioned that the hypoxic tumor microenvironment could be exploited as a targeting strategy. It was previously shown that these hypoxic areas have more reductive rather than the normal-cell oxidative metabolism (13), and we hypothesized that this property could be used to specifically target these tumor regions. It has long been recognized that 2-nitromidazole derivatives can selectively accumulate in hypoxic cells. We synthesize o new boronated derivative of 2-nitroimidazole:

B-381 had minimal cytotoxicity, preferentially accumulated in hypoxic cells, and demonstrated longer tumor retention in an in vivo glioma model compared to BPA. It achieved significant tumor/normal tissue ratios as well as tumor/blood ratios which are in compliance with the requirements for selective and successful BNCT. However, it presented relatively poor pharmacokinetics. B-381 presents a new class of BNCT agents in which their selectivity to tumors is based on tumor metabolism and biology.