A group of scientists from Moscow Institute of Physics and Technology (MIPT), the N.D. Zelinsky Institute of Organic Chemistry (RAS), the Institute of Developmental Biology (RAS), and the Institute of Cell Biophysics (RAS) are giving a new approach to novel agents with anticancer activity. They have formed a synthesis of compounds based on compounds extracted from parsley and dill seeds. They have posted their results of the study in the Journal of Natural Products.
The improvement of existing therapies and the search for new innovative approaches are essential components of a quest to treat cancer. The team developed a simple method of producing glaziovianin A and its structural analogs that inhibit the growth of human tumor cells, using feasible building blocks from nature. An evaluation of the agents in vivo using their validated sea urchin embryo assays yielded promising candidates affecting tubulin dynamics, according to MIPT professor Alexander Kiselev.
Chemotherapy is the main current method of medical treatment for cancer. This is the use of antimitotics, which inhibit the growth of cancer cells by disrupting the process of cell division. These cancer cells divide more frequently than normal cells and are more susceptible to effects of antimitotics. Melanoma cells double every 3 days but the number of their healthy progenitors melanocytes increase by 15%, even when cell division is stimulated. Antimitotics bind tubulin and affect microtubule dynamics disrupting cell cycle to result in arrested cell division and therefore selective death.
The potent antimitotic agent glaziovianin A, isolated from the leaves of the Brazilian tree, was focused on. The synthesis of this agent is laborious and requires expensive precursors and catalysts. A more efficient six-stage synthesis process was proposed. Precursors for the process were derived from the seeds of common plants, namely parsley and dill. Also a number of analogs were synthesized to help find analogues with favorable antimitotic properties. This activity was tested by two independent methods using the sea urchin embryos and human cancer cells.
The embryos of sea urchins were used to mimic actively dividing cells dependent on tubulin dynamics. Test substances were added to an aqueous medium with the embryos and determined the concentrations at which the rate of division changes and when it comes to a complete stop. The lower the concentration, the greater the antimitotic activity the substance has. By using the embryos, the scientists are able to determine several important parameters essential for an anti-cancer molecule in one shot. This effect can be easily observed using a common light microscope, including a specific antimitotic effect, solubility, overall toxicity and biomembrane permeability.
The antitumor effect of active molecules was studied with various human cancer cells, ex. Lung carcinoma, melanoma, prostate, breast, colon and ovarian cancers. The test substances were effective at limiting the growth of melanoma cells and non-toxic to healthy blood cells used as a control.
-Dr Fredda Branyon