The main objectives of the Action was to investigate mechanisms of multidrug resistance in bacteria, fungi, cancer cells, viruses and parasites and the following development of new drugs capable of reversing this drug resistance. The Action aimed at: * The synthesis of novel derivatives capable to reverse resistance in vitro and in vivo. * The investigation of molecular mechanism of resistance in cancer cells, parasites, bacteria, fungi and viruses. * The evaluation of prepared compounds The objectives have been reached, as proven by the astounding figure of 725 publications, with approximately half being joint publications. The noted close cooperation between MC members and expert associated groups has resulted in the synthesis of a large number of compounds which have been and are still analysed for their properties with respect to efflux pumps of micro-organisms, parasites and cancer. A European patent (1432717-”Substituted disiloxanes” methods for their manufacture and their use for reversing multidrug resistance) has been obtained in collaboration with LIPONOVA (Hamburg) by members of the the Humboldt University Berlin, Germany and University of Szeged, Hungary. Complemetary to the European Added Value of COST B16, through the networking of a large number of experts, the impact of COST B16 extented beyond the European continent for the purpose of evaluating results at the clinical level, a necessary requirement for the extension of these findings to the management of infectious diseases in Europe. Protocols involving the use of new and old compounds for the management of infectious diseases are now in progress in Africa (for malaria), in San Francisco (for a new variant CJD), in Argentina (for Multi-drug resistant Mycobacterium tuberculosis). One of the major achievements was the number of patents obtained for new compounds designed by MC members, like derivatives of phenothiazines (HU), the start of clinical trials for the use of phenothiazine for therapy of tuberculosis -to be implemented in Tanzania- coordinated by the NL MC members. The collaboration between members of COST B16 led to the succesful funding of an EU- RTN Marie Curie (MRTN-CT-2005-019335) on “Translocation”, together with other nationally-funded projects. Overall, the the defined goals have been met with the synthesis of novel compounds, their distribution to Action members and their evaluation and characterisation. The momentum created within the Action will continue as laboratory-proven activity of compounds will be taken further for animal studies and subsequent clinical trials for final demonstration of success hopefully leading to the promise to overcome antibiotic resistance in bacteria.
