Trioxacarcins are naturally occurring antibiotics that fight cancerous tumors and can serve as a building block towards producing other drugs and therapies. Their complex molecular structures have made them an attractive target in trying to synthesize them in the lab. They are normally extracted from Streptomyces bottropensis, and they are cytotoxic by means of attaching to double stranded DNA and actually modifying the covalent bonds of the genetic material. Unfortunately, most of these developed compounds don’t make it to the doctor’s office because of the severe side effects.
Scientists at Rice University — led by synthetic organic chemist K. C. Nicolaou — have developed a new process in synthesizing these trioxacarcins. His lab finds ways to replicate these trioxacarcins as well as other naturally occurring compounds so that they can be studied and used as a basis for a plethora of new potential medications. They are focused on fine tuning the structure to cause more damage to the tumor and less damage to the host in the form of the aforementioned side effects. The lab has been geared to figuring out the full structure of all the different variants of Trioxacarcins (DC-45-A1, A, D, C and C7”-epi-C for instance). A previous success in the antibody-drug conjugate (ADC) arena was in the form of Mylotarg, the first ADC to be approved by the FDA in 2000, which contained the potent natural product calicheamicin. Even though it was eventually withdrawn as a beneficial drug, the method by which it acts as a payload to target cancer cells via chemical linkers is now the focus of other studies.
Last year Nicolaou and his associates were responsible in synthesizing another potent antitumor agent known as shishimijicin A. Trioxacarcins may not be as potent as shishimijicin A, but are definitely more potent than Paclitaxel, a drug currently FDA approved to treat ovarian, breast, pancreatic and other cancers under the trade name Taxol. It has a bunch of side effects like hair loss, muscle and joint pains, and even diarrhea. Thus the pot at the end of the toxic rainbow would be easier to bear without these side effects making patients question whether the treatment is worth the trauma.Source: JACS