An efficient development method for anticancer drugs is the multi-component reaction, in which different reaction partners are combined in a reaction vessel, similar to cooking a stew. Because of the different possible combinations, compounds with varying properties can be synthesized in a single run.
In its original form, the anti-cancer drug chlorambucil (CLB) has strong side effects due to its lack of specificity and has therefore been replaced by other drugs in cancer therapy. The scientists used the multi-component reaction to give CLB new properties, aiming to improve effectiveness of the bioactive compound and reduce side effects.
In order to put this project into practice, specific macromolecules were included in the multi-component reaction. These macromolecules, in conjunction with a bioactive compound and various functional groups, can act as nanotransporters. With these transporters the active substances are to be brought directly to the site of action in the organism. As the macromolecule scaffold for such nanotransporters so-called Dendrimers, branched molecules that are reminding of tree branches, prove to be suitable (from the Greek dendron - the tree).
This combination of reaction components provided the scientists with a range of differently decorated CLB compounds that were then systematically tested against prostate cancer and colon cancer cell lines. One of the compounds studied proved to be particularly effective against prostate cancer cells. Initial tests also showed that this compound had no effect on healthy mouse connective tissue cells, where cell damage from the drug is undesirable.
With this study the researchers demonstrated that further development of the multi-component reaction can lead to the systematic optimization of known active substances. At the same time, numerous production steps are saved.
Original publication:
Nalin Seixas, Bruno Ravanello, Ibrahim Morgan, Goran Kaluđerović & Ludger Wessjohann, Chlorambucil Conjugated Ugi Dendrimers with PAMAM-NH2 Core and Evaluation of Their Anticancer Activity, published Feb. 2019 in Pharmaceutics 11/59, doi.org/10.3390/pharmaceutics11020059
