Maria Helena Garcia
Faculdade de Ciências da Universidade de Lisboa Universidade de Lisboa Portugal
Title: Ruthenium drugs for cancer therapy: small structural changes, different in vivo performances
Biography
Biography: Maria Helena Garcia
Abstract
In the recent years our group has been involved in the synthesis of new ruthenium organometallic complexes which cytotoxicity against several cancer cell lines was found, in most of the cases, better than that of cisplatin. In particular important IC50 values were found for the triple negative breast cancer (TNBC) and prostate cancer cells when treated with compounds which structures are based in the fragment “Ru(h5-C5H5)” with two different appended molecules.[1-2] Thus, three compounds of the panel were selected having in mind to understand any possible correlation between chemical structure and in vitro / in vivo activity. The main structural changes were the replacement of N,N by a N,O heteroaromatic ligand or inclusion of a sulphonate group in the phosphane ligand in order to increase water solubility. Although our in vitro studies such as cellular distribution, morphological alterations caused by drugs, binding to serum proteins, between others, revealed very similar responses for our selected drugs, their behaviour in vivo was completely different. While the therapeutic effect of one of these compounds evaluated in an orthotropic TNBC mouse model demonstrated the capacity to suppress tumour growth, not presenting the severe side-effects of other non-targeted chemotherapeutic agents, this was not the case of the other two compounds tested for prostate cancer. In fact, severe side effects were observed in the animals for one of the drugs while the other drug was excreted without exerting any effect neither in the animal nor in the tumour.