Synthesis of new aminoguanidinium and biguanidinium derivatives of ursolic and corosolic acids as potential antimicrobial agents.

The antibiotics and antifungal agents currently used in practical medicine are losing their effectiveness as a result of the rapid development of multidrug resistance in pathogenic microorganisms. In the context of this problem, modern medicine and veterinary medicine urgently need to discover new drugs and new medical technologies for the treatment of bacterial infections. Biological studies of pentacyclic triterpene acids, including ursolic and corosolic acids, over the last few decades have shown that these available secondary metabolites are active against many human bacterial and fungal pathogens. However, their antibacterial activity is much weaker compared to known anibiotics produced by bacteria and fungi. In order to enhance the antibacterial potential of natural tritepenes, we synthesised a series of new derivatives of ursolic and corosolic acids bearing aminoguanidinium and biguanidinium end fragments in the C-28 side chain. Guanidinium and biguanidinium groups are known to determine the chemical and physicochemical properties of biologically active substances. Many compounds containing guanidinium and biguanidinium moieties constitute an important class of therapeutic agents, including antibacterial and antifungal drugs. The introduction of guanidinium and biguanidinium moieties into triterpene acid molecules was carried out by guanylation and biguanylation of pre-synthesised carboxyamides of ursolic and corosolic acids containing terminal primary amino groups at C-28 of the alkane side chain. We found optimal guanylating and biguanylating reagents, which provided relatively mild reaction conditions and high yields of the target products.