Metal-Based Therapeutics for Leishmaniasis

Abstract

Figure 2. Structures of antimalarial drug chloroquine and antitrypanocidal drug benznidazole, and their respective metallo-derivatives, which show enhanced antiparasitic properties.

Chemistry and Some Biological Potential of Bismuth and Antimony Dithiocarbamate Complexes

“…As far back as 3500 BC, the Chinese and those in the Middle East made use of metal based drugs derived from gold and mercury chloride as a diuretic [20]. In the last century, specifically the early 1900s, Paul Elhrich used an arsenium based drug (arsenophenylglycine and arshphenamine) to treat trypanosoma disease (sleeping sickness) and syphilis, respectively [67]. This discovery birthed the development of 'metallodrugs' in that era, leading to more discoveries such as the use of sodium vanadate and derivatives of bismalltolato oxovanadium(IV) complexes for diabetics, and the use of gold based complexes such as aurothiomalate, auranofin, and aurothioglucose for rheumatoid arthritis [67].…”

“…In the last century, specifically the early 1900s, Paul Elhrich used an arsenium based drug (arsenophenylglycine and arshphenamine) to treat trypanosoma disease (sleeping sickness) and syphilis, respectively [67]. This discovery birthed the development of 'metallodrugs' in that era, leading to more discoveries such as the use of sodium vanadate and derivatives of bismalltolato oxovanadium(IV) complexes for diabetics, and the use of gold based complexes such as aurothiomalate, auranofin, and aurothioglucose for rheumatoid arthritis [67]. Despite this early potential demonstrated by these metal based drugs, they were continuously overlooked in favour of organic based drugs until the serendipitous discovery of a platinum based anticancer complex, called cisplatin, in 1969.…”

“…Despite this early potential demonstrated by these metal based drugs, they were continuously overlooked in favour of organic based drugs until the serendipitous discovery of a platinum based anticancer complex, called cisplatin, in 1969. This discovery drastically increased the study and the use of metal based therapy to date, and in turn has resulted in the development of medicinal inorganic chemistry as a mature research discipline [67]. The idea behind the design of metal based drugs is very commendable.…”

“…Many approaches have been used in the synthesis and the application of metal based drugs and one of the most frequently used approaches originates from the idea of metal-organic drug synergism, which gives rise to two main effects: (i) the enhancement of the biological activity of the organic part of the drug due to the presence of a metal ion, which may increase the residence time and thus allow the drug to reach its biological targets; and (ii) modulation of the toxicity often associated with metal ions due to the presence of the organic drug moiety, which allows the metal ion to get to the targeted sites and makes it less available for side and other damaging reactions [14,67,68]. A variety of metal complexes derived from different groups in the Periodic Table, especially the transition metals, have been extensively studied for biomedical applications [69].…”

Μελέτης της εποχιακής κατανομής των ειδών Phlebotomus που απαντώνται στην Κρήτη και του ρόλου τους στη μετάδοση του πρωτόζωου παράσιτου Leishmania, και μελέτη της διατήρησης της επίκτητης αντοχής του παράσιτου στα φάρμακα μέσα στους ξενιστές του

“…Τα μέταλλα στην ιατρική χρησιμοποιούνται εδώ και χιλιετίες (Caballero et al, 2014). Το tartar emetic ή antimony potassium tartrate, μια από τις πρώτες μορφές αντιμονίου, είναι ένα από τα πρώτα μεταλλικής φύσεως φάρμακα που χρησιμοποιήθηκαν για τη θεραπεία της λεϊσμανίασης.…”