In pursuit of new anti-malarial candidates: novel synthesized and characterized pyrano-benzodioxepin analogues attenuated Plasmodium berghei replication in malaria-infected mice.

Malaria, a parasitic disease, is one of the major causes of morbidity and mortality, particularly in the tropics. Following the increased resistance of the primary causative parasite, Plasmodium sp, to the mainstream drug, artemisinin combination therapies (ACTs), combating malaria incidences, morbidity and mortality have remained elusive. Novel pyrano-benzodioxepin derivatives (DHA-PABA and DHA-LEVO) were synthesized and characterized using Fourier transform infrared (FT-IR) and nuclear magnetic resonance (NMR) spectroscopies. The compounds were subjected to standard in vivo antimalarial screening (using chloroquine-sensitive strain) in mice, and the toxicity was also determined using a standard assay. The observed elevation in serum alkaline phosphatase and acid phosphatase activity in the untreated and the group administered lower doses of DHA-LEVO is an indication of the hepatic stage of the parasite in the experimental animal, which is accompanied by significant perturbation in the membrane of the hepatocyte leading to leakage of this enzyme out of the liver cells. The semisynthetic pyrano-benzodioxepin derivatives act rapidly by clearing the parasite load from the blood. The novel pyrano-benzodioxepin candidates containing endoperoxide functionality hold promise in the pursuit of new monotherapy drug candidates against the virulent strain of the plasmodium.

Biochemical and morphological changes in Trypanosoma brucei brucei-infected rats treated with homidium chloride and diminazene aceturate.

BACKGROUND: Chemotherapy which is one of the major methods for controlling trypanosomal infections is beset with several challenges including unwanted toxicity and limited efficacy. These factors and others underscore research efforts aimed at finding safer and more effective therapeutic agents for trypanosomiasis. Homidium chloride and diminazene aceturate are registered drugs for the treatment of animal trypanosomiasis. METHODS: Study investigated and compared, in an experimental Trypanosoma infection, the effects of two trypanocides on the pathology of tissues and some biochemical indices in rats. RESULTS: Data revealed that the levels of alkaline phosphatase, alanine transaminase and aspartate transaminase in infected positive animals were significantly (p<0.05) elevated relative to uninfected negative controls but showed no significant difference when compared with the trypanocide-treatment groups. The histopathological presentations in the infected and treatment groups are a demonstration of the inimical cellular alterations associated with Trypanosoma brucei brucei infection. CONCLUSIONS: The inimical alterations to biochemical and morphological parameters observed in the infected as well as the treatment groups is an implication suggesting shortcomings of the investigated trypanocides to alleviate pathology associated with Trypanosoma brucei brucei infection. We present evidence that further supports the urgent need for the development of safer and more effective trypanocides.

Changes in haematological indices and protein concentrations in Trypanosoma brucei infected rats treated with homidium chloride and diminazene aceturate.

Anaemia and immunosuppresion have been shown to be a cardinal feature in African trypanosomosis. In this study, we have evaluated and compared the capacity of two registered veterinary trypanocides Novidium® (homidium chloride) and Berenil® (diminazene aceturate) to reduce haematological and biochemical lesions in rats experimentally infected with T. brucei. Packed cell volume (PCV), lymphocyte and eosinophil values in infected negative control group were significantly different and lower compared to positive control group as well as infected animals treated with homidium chloride and diminazene aceturate (P<0.05). Also the white blood cell (WBC) and neutrophil counts in the negative control group were lower and significantly different from the other groups indicating evidence of infection-induced immunosuppresion. Haematological indices in infected rats treated with homidium chloride and diminazene aceturate were higher (P<0.05) than obtained in infected negative control group and significantly different from positive control (P<0.05). Total protein and albumin concentrations in infected negative control group were higher and significantly different from control and treated animals (P<0.05). In contrast, significantly lower values were obtained for albumin concentrations in treated animals compared to both negative and positive control groups (P<0.05). Results suggest that drugs administered have capacity to improved blood components as well as reverse immunosuppressive action of infecting trypanosomes.