Study of the biological potential of Anti-Schistosome Desloratandine Mansoni by molecular docking
INTRODUCTION: Schistosomiasis is a neglected disease that affects public health in underdeveloped countries. It is estimated that more than 206 million people in the world are affected by the disease and that 700 million live in risky places, causing about 200 thousand deaths annually. In Brazil, the Northeast region and the state of Minas Gerais are the areas most affected by schistosomiasis, with approximately 6 million people reported to be infected by the helminth parasite of the genus Schistosoma ssp, commonly known in Brazil as water belly, schistosis or disease of the snail. Currently the only drug with anti-schistosome action is prazinquantel, however, with reduced efficacy due to strains, it is increasingly resistant to treatment. Thus, it is increasingly necessary to search for new drugs that can contribute to the reduction of mortality affected by the parasite. In this sense, we seek to evaluate the potential of desloratadine against the key schistossoma mansoni protein. AIM: Thus, the study aimed to analyze the biological potential of anti-schistosome mansoni desloratadine and to elucidate molecular interactions through molecular docking. MATERIAL AND METHODS: Docking was performed using the Autodock Tools software, the receiver being considered rigid and the ligand flexible. A cubic box of 60 x 60 x 60 points was generated with a resolution of 0.357 Å between the grid points for the entire protein target. The methods used in docking were the Lamarckian genetic algorithm with global search and pseudo-Solis and Wets with local search. Other coupling parameters were defined with standard values and the analyzes were concentrated on the conformation of less binding free energy. RESULTS: The docking of desloratadine with the target protein Uridine Phosphorylase (UP) obtained free binding energy of -8.45 Kcal.mol-1 and an inhibition constant of 640.68 nM. This interaction did not show hydrogen bonding, however, there is an intense interaction at the UP protein active site in the amino acid residues Arg121, Gln201, Glu234, Glu232, Gly126, Met93, Met233, Met231, Phe272, Phe197, Ser125 and Thr124 that perform hydrophobic interactions. CONCLUSION: Desloratadine obtained attractive results in relation to the effectiveness of the molecular fitting to schistossoma mansoni UP protein, demonstrating molecular affinity and biological potential to inhibit it and lead to damage to the worm. Thus, we recommend in vitro studies to elucidate its inhibitory action on Shistossoma mansoni cells.
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