Synthesis of a Novel Combretastatin A4 Analog with a 5,6,7-Trimethoxy Indole Substituted at the 3-Position

Teresa Rocha

Abstract


Combretastatin A4 (CA4) is an effective anti-cancer drug that works by inhibiting tubulin formation and thus decreases cellular growth. Inhibition of tubulin formation also triggers a pathway in the cell that induces a change in cell shape. The deformation of cells in tumor vasculature systems block blood flow and selectively kill tumors. Due to CA4’s efficacy against various cancer cell lines, including multidrug resistant cell lines, and due to problems with the drug, such as its low water solubility, further investigations on CA4 analogs are being pursued. Not an uncommon feature for these analogs is the utilization of an indole ring. Indoles are highly biologically active molecules and are used in a broad range of pharmaceuticals. Past researchers in Dr. Holt’s lab group identified the need to substitute a trimethoxy indole in place of CA4’s trimethoxy benzene ring, binding the group at the indole’s 2-position. Due to the prominence of indoles being substituted at their 3-position in nature, such as the amino acid L-tryptophan, a CA4 analog is being pursued in which a trimethoxy indole is bound at its 3-position in place of the trimethoxy benzene ring. This placement will be performed utilizing halogenation, coupling and dehydrogenation reactions. Presently, both rings to make the intended analog have been synthesized and work is being pursued towards their coupling and then subsequent reduction which should create the desired analog.


Keywords


Chemotherapy; Cancer; Combretastatin A4; Indole

Full Text: PDF

Refbacks

  • There are currently no refbacks.