| Autor: |
Abdulrashid NI; Department of Biochemistry, Ahmadu Bello University, Zaria 810241, Nigeria., Aminu S; Department of Biochemistry, Ahmadu Bello University, Zaria 810241, Nigeria., Adamu RM; Department of Biotechnology, School of Engineering and Technology, Sharda University, Greater Noida 201310, India., Tajuddeen N; Department of Chemistry, Ahmadu Bello University, Zaria 810241, Nigeria., Isah MB; Department of Biochemistry, Umaru Musa Yar'adua University, Katsina 820241, Nigeria., Jatau ID; Department of Veterinary Parasitology and Entomology, Ahmadu Bello University, Zaria 810241, Nigeria., Aliyu AB; Department of Chemistry, Ahmadu Bello University, Zaria 810241, Nigeria., Simelane MBC; Department of Biochemistry, University of Johannesburg, Johannesburg 2001, South Africa., Onyike E; Department of Biochemistry, Ahmadu Bello University, Zaria 810241, Nigeria., Ibrahim MA; Department of Biochemistry, Ahmadu Bello University, Zaria 810241, Nigeria. |
| Abstrakt: |
Sub-Saharan Africa is profoundly challenged with African Animal Trypanosomiasis and the available trypanocides are faced with drawbacks, necessitating the search for novel agents. Herein, the chemotherapeutic potential of phloroglucinol on T. congolense infection and its inhibitory effects on the partially purified T. congolense sialidase and phospholipase A 2 (PLA 2 ) were investigated. Treatment with phloroglucinol for 14 days significantly ( p < 0.05) suppressed T. congolense proliferation, increased animal survival and ameliorated anemia induced by the parasite. Using biochemical and histopathological analyses, phloroglucinol was found to prevent renal damages and splenomegaly, besides its protection against T. congolense -associated increase in free serum sialic acids in infected animals. Moreover, the compound inhibited bloodstream T. congolense sialidase via mixed inhibition pattern with inhibition binding constant (Ki) of 0.181 µM, but a very low uncompetitive inhibitory effects against PLA 2 (Ki > 9000 µM) was recorded. Molecular docking studies revealed binding energies of -4.9 and -5.3 kcal/mol between phloroglucinol with modeled sialidase and PLA 2 respectively, while a 50 ns molecular dynamics simulation using GROMACS revealed the sialidase-phloroglucinol complex to be more compact and stable with higher free binding energy (-67.84 ± 0.50 kJ/mol) than PLA 2 -phloroglucinol complex (-77.17 ± 0.52 kJ/mol), based on MM-PBSA analysis. The sialidase-phloroglucinol complex had a single hydrogen bond interaction with Ser453 while none was observed for the PLA 2 -phloroglucinol complex. In conclusion, phloroglucinol showed moderate trypanostatic activity with great potential in ameliorating some of the parasite-induced pathologies and its anti-anemic effects might be linked to inhibition of sialidase rather than PLA 2 . |
