Applications of antimony drugs as antileishmanial agents

Chemo Secrets From a Breast Cancer Survivor

Breast Cancer Survivors

Get Instant Access

Antimony-based drugs have remained the major therapeutic treatment in the clinic for decades.19 The use of antimony chemotherapy increases the survival rate of those patients with Leishmania infection to over 90%.20 Although its main action is concentrated only on the visceral leishmaniasis, other forms of the disease are also responsive. The major disadvantages are a long treatment period, requiring hospitalization, and the need in many cases for subsequent course of treatment for an effective clinical cure in certain areas. The first anti-leishmanial drug, PAT (Tartar emetic®) was developed around 1910.18,21,22 In spite of increasing the survival rate, the agent was highly toxic to humans. Several other antimony compounds including antimony bis(4,5-dihydroxybenzene-3,5-disulphonate)

Figure 23.2 Proposed structures of clinically used SbV drugs: (a) Pentosam and (b) Glucantime

Figure 23.2 Proposed structures of clinically used SbV drugs: (a) Pentosam and (b) Glucantime

(Stibophen®), meglumine antimonate (Glucantime®), sodium antimony(III) gluconate (Triostam®) and sodium stibogluconate (Pentosam®), have also been used clinically for the treatment of different forms of leishmaniasis. Since penta-valent antimonials have a more efficient therapeutic index and are 10 times less toxic to humans than their trivalent analogues, they have become the first choices of chemotherapy.23 25 The carbohydrates in the drugs increase the solubility of antimony and are responsible for the delivery of the antimony to the macrophages, where the protozoa that cause leishmaniasis undergo division. Sodium stibogluconate is an SbV complex of a carbohydrate (gluconic acid) and was first used for the treatment of Leishmania during the mid-1930s26 and is still predominantly used in English-speaking countries.20 The structure of the complex remains unknown. It is commonly believed that the agent contains only one 746 Da species, probably a dimer, with two Sb111 linked by an oxygen (Figure 23.2).27 However, polymeric species with molecular weight up to 4kDa may also be present in solution.28

Meglunmine antimonate has also been used as the first-choice drug predominantly in French- and Spanish-speaking countries.20 A series of oligomers of antimony and N-methyl-D-glucamine (NMG) has been observed with the general formula of Sbn(NMG)n+1 or Sbn(NMG)n.29 The major component of meglunmine antimonate is Sb(NMG)2, with a formula mass of 507 Da. The proposed basic structures of the two drugs are shown in Figure 23.2.

Was this article helpful?

0 0
10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

Get My Free Ebook

Post a comment