AIDS patients, transplant recipients, and other immunocompromised individuals are susceptible to numerous opportunistic infections, such as the one caused by the fungal pathogen Cryptococcus neoformans. Initial pulmonary infection is believed to lead to Cryptococcal meningitis, which even if treated, is often fatal. AIDS patients are unlikely to survive C. neoformans infections, with 10-week survival rates as low as 40%. Leishmaniasis, another disease caused by infection with a pathogen (in this case, a parasite of the genus Leishmania), is among the major debilitating and devastating tropical diseases that are targets for the World Health Organization’s special program Research and Training in Tropical Diseases and most recently the Drugs for Neglected Diseases initiative. These diseases are caused by the parasites of the genus Leishmania. Overall, the demand for chemotherapeutic agents for the treatment of cryptococcal meningitis and leishmaniasis is desperate. Our previous work has focused on the synthesis and biological activity of the transition metal complexes of linked, bridged tetraazamacrocycles and many derivatives have been shown to act as anti-viral agents, CXCR4 chemokine receptor antagonists, and as biological imaging agents. In the present work, screening of a library of these ligands and complexes has revealed that certain of these novel compounds possess one or more anti-microbial activities including anti-fungal activity against C. neoformans and anti-parasitic activity against Leishmania parasites. We will present structures and anti-microbial activities of a large family of linked, bridged tetraazamacrocycles and their transition metal complexes. Many of these compounds demonstrated IC50 values well below the established therapeutic standards for the clinical treatment of C. neoformans infections and leishmaniasis.

Antifungal and anti-parasitic transition metal complexes of linked, bridged tetraazamacrocycle

251st National Meeting (2016)

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