University of North Carolina at Asheville
Subject Listing - Chemistry
Advisor: Dr. Herman L. Holt, Jr., Dr. Ted Meigs
Friday, Oral Session 5, Presentation 3, Karpen Hall 038
SYNTHESIS AND BIOACTIVITY OF ANTI-TUMOR COMBRETASTATIN ANALOGUES
Since the isolation and characterization of the anti-tumor agent combretastatin A-4 from the African bushwillow tree Combretum caffrum (Combretaceae), a large family of synthetic combretastatin analogues has been produced that show great potential for use as chemotherapy drugs. The combretastatins slow tumor growth and reduce cellular function by proceeding through the same mode of action as the natural product colchicine. Colchicine and the combretastatins (natural and synthetic) are excellent disruptors of the cellular cytoskeleton, which is composed of microtubules. Microtubules are polymers of the proteins α and β tubulin, and the combretastatins inhibit their polymerization. The cytoskeleton controls the arrangement and movement of organelles in a cell, as well as many of the processes involved in mitosis (cellular replication). Since the combretastatins inhibit the formation of the cytoskeleton, many cellular functions are halted by the combretastatins, effectively reducing tumor growth and size. This study aims to produce novel combretastatin analogues that contain functional groups new to the combretastatin family of compounds. The ethene group that bridges the two phenyl rings of the combretastatins is aimed to be replaced with an aziridine group as well as an azirine group. The aziridine and azirine groups are hypothesized to increase the activity of the compounds by increasing water solubility as well as general reactivity. Bioassay studies will determine how effective these new compounds are versus other combretastatins and compounds currently used in chemotherapy. Specifically, K562 cells (human myelogenous leukemia), MDA-MB-435 cells (human breast cancer) and SW480 cells (human colon adenocarcinoma) are to be tested with the compounds produced.
Advisor: Dr. Herman L. Holt, Jr., Assistant Professor, Department of Chemistry, University of North Carolina at Asheville, Asheville, NC
Advisor: Dr. Ted Meigs, Assistant Professor, Department of Biology, University of North Carolina at Asheville, Asheville, NC