AABRE: NETWORKING IN PUERTO RICO
PR-AABRE Researcher: Beatriz Zayas, Ph.D., School of Environmental Affairs, Universidad Metropolitana
AABRE Cluster: Drug Design and Delivery
Collaborators: Antonio Alegría, Ph.D. (UPR, Humacao Campus); Osvaldo Cox, Ph.D. (UMET); Dr. John Essigmann, Ph.D. (MIT)
Mentor: Fernando González, Ph.D. (UPR, Río Piedras Campus)
Title of AABRE Project: DNA Interaction and Mutational Activity of Novel Benzazolo [3, 2, -a] Quinolinium Salts Anticancer Drugs
RESEARCHERS AT THREE UNIVERSITIES in Puerto Rico are studying four potential anticancer compounds. To understand how they work and how effective they are, molecular toxicologist Beatriz Zayas, professor of the School of Environmental Affairs at Universidad Metropolitana (UMET), and her student research team are testing them in vitro with a new analytical methodology.
Synthesized by Dr. Osvaldo Cox and UMET students, the compounds belong to a new family of synthetic cationic (positively charged) alkaloids known as nitrobenzazolo [3,2-a] quinolinium salts (BQS’s). The researchers are focusing their efforts on four new nitro containing BQS derivatives: NBQ-25, NBQ-38, NBQ-59, and NBQ-97. They believe that these compounds could become effective anticancer drugs, depending on their reduction of the nitro group and their ability to bind covalently to DNA. Covalent and permanent binding with DNA can cause lesions on a cancer cell, which could lead to its death. The compounds may also be good candidates for intramitochondrial retention, which would enhance their interaction with DNA in tumor cells.
Zayas and students recently developed an analytical methodology based on high–performance liquid chromatography mass spectrometry method (HPLC-MS) that will allow them to monitor and analyze the new drugs’ interaction with DNA. HPLC-MS is a technique that can help characterize a molecule by its polarity and molecular mass weight. Zayas and her collaborators are also working on optimizing the appropriate cell culture environment and conditions to grow tumor cells in order to observe the direct effect of these compounds on cancer cells.
“We take DNA from calf thymus or from treated cells in culture to see if the compounds covalently bind with the DNA. Covalent binding is one way that a drug can kill cancer or normal cells. Does the covalent adduct remain or induce a permanent damage? The next step is to evaluate these compounds once they cross the cell membrane and bind to the DNA to see if they can generate a mutation and/or lethal effect to the cancer cell. A mutation is an alteration on the normal sequence of the DNA, which can result in the modification or absence of a protein. These changes can transform cells or inhibit their growth.
“Our long-term goal is to generate enough data for additional research that will allow us to test these drugs on animals and contribute to the battle against cancer by generating new and effective anticancer drugs.”
bzayas@mail.suagm.edu
