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

Kashif, Muhammad; Villalobos-Rocha, Juan Carlos; Nogueda‐Torres, Benjamín; Pérez‐Villanueva, Jaime; Rodríguez‐Villar, Karen; Medina-Franco, José L.; Andrade, Peterson de; Carvalho, Ivone; Rivera, Gildardo

doi:10.3390/molecules22111863

Cited by 14 publications

(9 citation statements)

References 51 publications

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“…The validated drugs in this study were potently effective against the trypomastigote but not the epimastigote form. This behavior can be explained by the morphological differences between the two stages of T. cruzi and has already been observed in previous studies [ 96 , 97 , 98 ]…”

Section: Discussionsupporting

confidence: 76%

Repositioned Drugs for Chagas Disease Unveiled via Structure-Based Drug Repositioning

Adasme

Bolz

Adelmann

et al. 2020

IJMS

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Chagas disease, caused by the parasite Trypanosoma cruzi, affects millions of people in South America. The current treatments are limited, have severe side effects, and are only partially effective. Drug repositioning, defined as finding new indications for already approved drugs, has the potential to provide new therapeutic options for Chagas. In this work, we conducted a structure-based drug repositioning approach with over 130,000 3D protein structures to identify drugs that bind therapeutic Chagas targets and thus represent potential new Chagas treatments. The screening yielded over 500 molecules as hits, out of which 38 drugs were prioritized following a rigorous filtering process. About half of the latter were already known to have trypanocidal activity, while the others are novel to Chagas disease. Three of the new drug candidates—ciprofloxacin, naproxen, and folic acid—showed a growth inhibitory activity in the micromolar range when tested ex vivo on T. cruzi trypomastigotes, validating the prediction. We show that our drug repositioning approach is able to pinpoint relevant drug candidates at a fraction of the time and cost of a conventional screening. Furthermore, our results demonstrate the power and potential of structure-based drug repositioning in the context of neglected tropical diseases where the pharmaceutical industry has little financial interest in the development of new drugs.

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Section: Discussionsupporting

confidence: 76%

Repositioned Drugs for Chagas Disease Unveiled via Structure-Based Drug Repositioning

Adasme

Bolz

Adelmann

et al. 2020

IJMS

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“…When computational strategies screened more than 3000 drugs approved by the Food and Drug Administration (FDA), and in vitro and in vivo tests were performed, it was seen that the anti-inflammatory sulfasalazine ( Figure 1F ) can be used as a lead to design new enzyme inhibitor drugs (Lara-Ramirez et al, 2017). Recently, it was found that molecules containing amide, hydroxyl, and carboxylic acid radicals in their aromatic rings can enhance the biological activity of these enzyme inhibitors, which may lead to a better rational drug design (Kashif et al, 2017).…”

Section: Synthetic Drugs and New Therapeutic Approaches For Chagas DImentioning

confidence: 99%

Chagas Disease Treatment and Rational Drug Discovery: A Challenge That Remains

et al. 2019

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“…Benzoic acid and its derivatives have shown antibacterial activity and assisted in the removal of exfoliated cells. Discovered to be eligible for Chagas disease treatment through different biological mechanism and also show significant trypanocidal activity [5]. Reaction involving isatoic anhydride, amine and benzyl E.E.…”

Section: Introductionmentioning

confidence: 99%

One-pot synthesis of N-benzyl-2-aminobenzoic acid, via ring opening of isatoic anhydride derivative, and its antibacterial screening

Odion¹,

Ajibosin²,

Usifoh³

2021

J. Pharm Bio.

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2-(N-Benzyl) amino benzoic acid is a bifunctional molecule that could be produced from the reaction between isatoic anhydride and aryl halide. Analogues and derivatives of isatoic anhydride have wide application in pharmaceuticalsincluding antibacterial activity. The aim of this study is to synthesize, characterize and screen N-benzyl isatoic anhydride and 2-(N-benzyl) amino benzoic acid for antibacterial activity. The reaction of isatoic anhydride and benzyl bromide in the presence of potassium carbonate in DMSO at room temperature yielded N-benzyl isatoic anhydride, which under hydrolysis yielded 2-(N-benzyl) amino benzoic acid in which the anhydride ring is opened up. This compound was screened against Gram positive and negative bacteria. Moderate yield of 2-(N-benzyl) amino benzoic acid, a yellow crystal (melting point of 160-162oC, percentage yield 65 %, Rf 0.19) formed by ring opening of N-benzyl isatoic anhydride. The compound showed no antibacterial activity against Escherichia coli, Staphylococcus aureus, Pseudomonas pyocyanea, Salmonella typhimurium, Klebsiella aeruginosa and Bacillus subtilis. 2-(N-benzyl)amino benzoic was synthesized, characterized and showed no activity against bacteria.

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

Cited by 14 publications

References 51 publications

Repositioned Drugs for Chagas Disease Unveiled via Structure-Based Drug Repositioning

Repositioned Drugs for Chagas Disease Unveiled via Structure-Based Drug Repositioning

Chagas Disease Treatment and Rational Drug Discovery: A Challenge That Remains

One-pot synthesis of N-benzyl-2-aminobenzoic acid, via ring opening of isatoic anhydride derivative, and its antibacterial screening

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