Benzoic Acid Derivatives with Trypanocidal Activity: Enzymatic Analysis and Molecular Docking Studies toward Trans-Sialidase

Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry
Muhammad KashifGildardo Rivera

Abstract

Chagas, or American trypanosomiasis, remains an important public health problem in developing countries. In the last decade, trans-sialidase has become a pharmacological target for new anti-Chagas drugs. In this work, the aims were to design and find a new series of benzoic acid derivatives as trans-sialidase (TS) inhibitors and anti-trypanosomal agents. Three compounds (14, 18, and 19) sharing a para-aminobenzoic acid moiety showed more potent trypanocidal activity than the commercially available drugs nifurtimox and benznidazole in both strains: the lysis concentration of 50% of the population (LC50) was <0.15 µM on the NINOA strain, and LC50 < 0.22 µM on the INC-5 strain. Additionally, compound 18 showed a moderate inhibition (47%) on the trans-sialidase enzyme and a binding model similar to DANA (pattern A).

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Citations

Aug 21, 2019·Frontiers in Pharmacology·Ana Catarina Cristovão SilvaMarcelo Zaldini Hernandes
Jun 13, 2019·Current Medicinal Chemistry·Leandro S SangenitoAndré L S Santos
Nov 26, 2020·International Journal of Molecular Sciences·Melissa F AdasmeMichael Schroeder

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Methods Mentioned

BETA
column chromatography

Software Mentioned

AutoDock Tools
YASARA
PyMOL
Maestro
UCSF Chimera
AutoDock Vina
GraphPad Prism

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