The trans-sialidase enzyme plays a key role to enhance the virulence of trypanosoma cruzi for Chagas disease, by transfer of sialic acid from host to parasite surface. In this work we designed and synthesised novel β-amino acids derivatives. The molecular docking study showed, the compounds M-11, N-11 has the highest binding energies (-11.1 kcal/mol) as compared to reference DANA (-7.8 kcal/mol), the natural ligand of trans-sialidase. The 3D and 2D analysis of these compounds in catalytic pocket of the enzyme, showed the hydrogen bond, pi-pi stacking, pi anion, hydrophobic & van der waals interaction with all important amino acid residues (Arg35, Arg245, Arg314, Tyr119, Trp312, Tyr342, Glu230 and Asp59). In vitro trypanocidal activity were evaluated, on trypomastigotes of NINOA & INC-5 strains, which showed that compounds with electron donating groups support the NINOA, with maximum lysis 85% and electron withdrawing group showed the higest lysis about 80% lysis in INC-5. Furthermore, compound 11in series M, N, & O showed the 65-68 % lysis in both strains which is higher than reference drugs nifurtimox and benznidazole (28-49%). The enzyme inhibition assay of selected compounds was determined by using high performance ion exchange chromatography with pulse amperometric detection. Compound M-11 & M-4 showed the 86.9% & 82.5% enzyme inhibition. A good correlation between docking and enzyme inhibition was also found.

Synthesis of new β-amino acids derivatives as anti trypanocidal agent and docking & Inhibition study on trans-sialidase enzyme

255th National Meeting (2018)

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