Biokoniugaty antybiotykow jonoforowych : cele, strategie syntezy i właściwości
Journal Title: Wiadomości Chemiczne - Year 2018, Vol 72, Issue 1
Abstract
Polyether ionophore antibiotics (ionophores) represent a large group of naturally- occurring lipophilic compounds which are able to form complexes with the metal cations and transport them across the lipid membranes. This process disturbs the intercellular Na+/K+concentration gradient and intracellular pH, and leads to the mitochondrial damages, cell swelling, vacuolization and finally to apoptosis process. For this reason, ionophores are commonly used in veterinary medicine as the non-hormonal growth-promoting as well as coccidiostatic agents. In this group particularly interesting are monensin and salinomycin (Fig. 1) because of their proved anti-tumour activity, including efficiency against multidrug- -resistant cancer cells and cancer stem cells of different origin. Improved synthetic derivatives of both polyether ionophores are thus of considerable current interest. Selective derivatization of these structures whose display multiple reactive functional groups and, in the case of salinomycin, a sensitive tricyclic spiroketal ring system is however non-trivial. Even so, semi-synthetic analogs reported to date includes i.a. selective derivatization of the carboxyl group, the three hydroxyl groups, the ketone group, the alkene, and epimerization of the characteristic tricyclic salinomycin unit (for more details see: M. Antoszczak, A. Huczyński, B. Brzezinski, Wiad. Chem., 2017, 71, 629). On the other hand, as part of the original program to develop innovatory anti- -cancer pro-drugs and prompted by the idea that cancer cells may be individually effectively killed by monensin and salinomycin, a very interesting direction of research is bioconjugation of these ionophores. In this context, our review article is focused on the possible role of hybrids of both ionophore antibiotics with other biologically active substances (natural amino acids, Cinchona alkaloids, flavonoids, nucleosides) in anti-bacterial and anti-cancer treatment, and gives an overview of their properties.
Authors and Affiliations
Michał Antoszczak, Marta Kordylas, Adam Huczyński
Keywords
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