Reactive Oxygen Species (ROS)-Activated Prodrugs: Phenylboronic Acid Nitrogen Mustards
Mentor 1
Xiaohua Peng
Start Date
28-4-2023 12:00 AM
Description
Nitrogen mustard containing compounds cause DNA cross-linking that ceases DNA replication and leads to cell death upon metabolism. This mechanism causes these drugs to be more efficient in cancer treatment than standard chemotherapy practices. We have concluded that two Phenylboronic acid nitrogen mustard prodrugs, CWB-20145 and FAN-NM-CH3 reduce tumor sizes due to the prodrugs’ enhanced activity when partnered with hydrogen peroxide (H2O2). Although initially inactive, prodrugs become activated upon metabolism. Due to the increase level of reactive oxygen species (ROS), including H2O2, present in cancer cells, these prodrugs can be selective to cancer cells and less toxic to normal cells. In vitro testing on protein expression levels, including tumor suppressor p53, has let us investigate biological pathways in cancerous cells that are untreated versus drug treated. This was done using RT-qPCR to amplify RNA upon extracting mRNA from either type of cancer cell. A series of in vivo experiments have also determined that the prodrugs are safe in mice.
Reactive Oxygen Species (ROS)-Activated Prodrugs: Phenylboronic Acid Nitrogen Mustards
Nitrogen mustard containing compounds cause DNA cross-linking that ceases DNA replication and leads to cell death upon metabolism. This mechanism causes these drugs to be more efficient in cancer treatment than standard chemotherapy practices. We have concluded that two Phenylboronic acid nitrogen mustard prodrugs, CWB-20145 and FAN-NM-CH3 reduce tumor sizes due to the prodrugs’ enhanced activity when partnered with hydrogen peroxide (H2O2). Although initially inactive, prodrugs become activated upon metabolism. Due to the increase level of reactive oxygen species (ROS), including H2O2, present in cancer cells, these prodrugs can be selective to cancer cells and less toxic to normal cells. In vitro testing on protein expression levels, including tumor suppressor p53, has let us investigate biological pathways in cancerous cells that are untreated versus drug treated. This was done using RT-qPCR to amplify RNA upon extracting mRNA from either type of cancer cell. A series of in vivo experiments have also determined that the prodrugs are safe in mice.
