AABRE: NETWORKING IN PUERTO RICO
PR-AABRE Researcher: Cesar Lozano, Ph.D., Department of Chemistry and Physics, University of Turabo
Cluster: Drug Design and Delivery
Collaborator: Fernando González, Ph.D. (UPR, Río Piedras Campus)
Mentor: John Soderquist, Ph.D. (UPR, RP)
Project Title: Synthesis, Characterization, Anticancer Activity and Reactivity
Toward Biological Targets of New Platinum (II) Complexes
CANCER TREATMENTS with metal-based drugs have been in practice for many years, but they could become more effective and produce fewer side effects once scientists discover the molecular basis of their cytotoxicity. Chemist and Chair of the Department of Chemistry and Physics at the University of Turabo Cesar Lozano and his team of student researchers have synthesized new platinum compounds and are researching exactly how the drugs work at the molecular level.
“In nature, platinum is found very pure as a metal, but chemists can synthesize platinum complexes. We begin with one compound and chemically change it.”
Currently cisplatin is the most commonly used metal-based anticancer agent, but it causes side effects such as anemia, bladder infections, liver problems, and loss of hair. “The problem is that they aren’t very water soluble and not very specific—they kill both tumor and healthy cells,” says Lozano.
Drug cytotoxicity can be measured by the loss of cell viability, DNA fragmentation, extent of DNA platination, and impairment of cellular mitochondrial oxygen consumption. Most metal anticancer drugs interact with cells by altering the DNA in one of three ways: 1) intercalation, in which the compound deforms the DNA helix and it can not reproduce itself; 2) covalent linking, in which the compound forms a bond with a DNA base and acts like a ligand (a kind of molecular glue); and 3) break up the DNA. “Some iron compounds break up the DNA, but this isn’t used much anymore because it is too invasive—there are too many side effects,” says Lozano. “Our compounds, anionic trihalo complexes of platinum (II) and neutral platinum (II), we believe, do intercalation and covalent linking at the same time. In other words, they are bifunctional compounds.” This makes the drugs more effective against tumor cells.
“After we have synthesized and purified the platinum–based ligands, we characterize them, using various spectrophotometric methods including NMR, FTIR, UV-Vis, as well as elemental analysis. Then they are sent to the Biotesting Laboratory at UPR, RP to Dr. Gonzalez’ lab to be tested for anticancer activities and the minimum amount of the compound necessary to kill the cancer cells.” The interaction with DNA is studied in promising compounds. This gives the researchers insight into the mechanism by which the drugs act.
“At this point, we study the interaction of the altered DNA with certain proteins. Certain proteins in our body act by binding with platinum compounds and then are eliminated in the blood.” This would reduce the side effects of metal-based chemotherapy. Eventually, Lozano would like to see the synthesized platinum drugs being used against cancerous tumors.
clozano@suagm.edu
