Single-step synthesis and in vitro anti-mycobacterial activity of novel nitrofurantoin analogues

Zuma, Nonkululeko H.; Smit, Frans J.; Seldon, Ronnett; Aucamp, Janine; Jordaan, Audrey; Warner, Digby F.; N’Da, David D.

doi:10.1016/j.bioorg.2020.103587

Cited by 17 publications

(16 citation statements)

References 52 publications

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“…Nitrofurantoin shows extremely low lipophilicity (clogP −0.22), which may explain its poor trypanocidal activity, as it cannot efficiently permeate parasitic biomembranes. In contrast, analogs 1 and 2 have low cLogP values of −0.04 and 0.36, respectively [ 11 ], which are relatively higher than those of nitrofurantoin, suggesting their moderately lipophilic nature. They were found to possess moderate (0.19–0.73 µM) activity against the T. b. rhodesiense Chirundu and T. congolense IL3000 strains.…”

Section: Discussionmentioning

confidence: 99%

“…Nitrofurantoin is a hypoxic agent with activity against a myriad of anaerobic pathogens. This nitrofuran compound contains a Schiff base derived from 5-nitrofuraldehyde, which is known to be effective against a wide spectrum of gram-positive and gram-negative bacteria and various pathogens, including trypanosomes [ 10 , 11 ]. Nitrofurantoin analogs show good safety profiles, enhanced anti-mycobacterial potency, improved lipophilicity, and a reduced protein-binding affinity.…”

Section: Introductionmentioning

confidence: 99%

“…Nitrofurantoin analogs show good safety profiles, enhanced anti-mycobacterial potency, improved lipophilicity, and a reduced protein-binding affinity. Nitrofurans are broad-spectrum redox-active antibiotics, with dose-dependent bacteriostatic or bactericidal activity [ 10 , 12 ], and have been used in animal feeds, pharmaceuticals, and other applications [ 11 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

“…The clinical drug furazolidone belongs to the group of nitrofuran antibiotics and has been widely used as an antibacterial and antiprotozoal feed additive for poultry, cattle, and farmed fish [ 11 , 14 ]. Nifurtimox, another nitrofuran derivative, which was developed in the 1960s, has been used to treat Chagas disease caused by T. cruzi .…”

Section: Introductionmentioning

confidence: 99%

“…More recently, the combination of nifurtimox and eflornithine was evaluated for the treatment of late-stage T. b. gambiense sleeping sickness [ 15 , 16 , 17 ]. Furthermore, a study revealed that chemically synthesized analogs of nitrofurantoin had significantly enhanced antimycobacterial activity [ 11 ]. Overall, these reports suggest that some nitrofurantoin analogs can be used against African trypanosomes.…”

Section: Introductionmentioning

confidence: 99%

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In Vitro and In Vivo Trypanocidal Efficacy of Synthesized Nitrofurantoin Analogs

et al. 2021

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African trypanosomes cause diseases in humans and livestock. Human African trypanosomiasis is caused by Trypanosoma brucei rhodesiense and T. b. gambiense. Animal trypanosomoses have major effects on livestock production and the economy in developing countries, with disease management depending mainly on chemotherapy. Moreover, only few drugs are available and these have adverse effects on patients, are costly, show poor accessibility, and parasites develop drug resistance to them. Therefore, novel trypanocidal drugs are urgently needed. Here, the effects of synthesized nitrofurantoin analogs were evaluated against six species/strains of animal and human trypanosomes, and the treatment efficacy of the selected compounds was assessed in vivo. Analogs 11 and 12, containing 11- and 12-carbon aliphatic chains, respectively, showed the highest trypanocidal activity (IC50 < 0.34 µM) and the lowest cytotoxicity (IC50 > 246.02 µM) in vitro. Structure-activity relationship analysis suggested that the trypanocidal activity and cytotoxicity were related to the number of carbons in the aliphatic chain and electronegativity. In vivo experiments, involving oral treatment with nitrofurantoin, showed partial efficacy, whereas the selected analogs showed no treatment efficacy. These results indicate that nitrofurantoin analogs with high hydrophilicity are required for in vivo assessment to determine if they are promising leads for developing trypanocidal drugs.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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In Vitro and In Vivo Trypanocidal Efficacy of Synthesized Nitrofurantoin Analogs

et al. 2021

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Surface Immobilization of Oxidized Carboxymethyl Cellulose on Polyurethane for Sustained Drug Delivery

Somani,

Verma,

Nonglang

et al. 2024

Macromolecular Bioscience

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Polyurethane (PU) has a diverse array of customized physical, chemical, mechanical, and structural characteristics, rendering it a superb option for biomedical applications. The current study involves modifying the polyurethane surface by the process of aminolysis (aminolyzed polyurethane; PU‐A), followed by covalently immobilizing Carboxymethyl cellulose (CMC) polymer utilizing Schiff base chemistry. Oxidation of CMC periodically leads to the creation of dialdehyde groups along the CMC chain. When the aldehyde groups on the OCMC contact the amine group on a modified PU surface, they form an imine bond. Scanning electron microscopy (SEM), contact angle, and X‐ray photoelectron spectroscopy (XPS) techniques are employed to analyze and confirm the immobilization of OCMC on aminolyzed PU film (PU‐O). The OCMC gel incorporates Nitrofurantoin (NF) and immobilizes it on the PU surface (PU‐ON), creating an antibacterial PU surface. The confirmation of medication incorporation is achieved using EDX analysis. The varying doses of NF have demonstrated concentration‐dependent bacteriostatic and bactericidal effects on both Gram‐positive and Gram‐negative bacteria, in addition to sustained release. The proposed polyurethane (PU‐ON) surface exhibited excellent infection resistance in in vivo testing. The material exhibited biocompatibility and is well‐suited for biomedical applications.

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Synthesis and fungicidal activity of methyl (E)-1-(2-((E)-2-methoxy-1-(methoxyimino)-2-oxoethyl)benzyl)-2-(1-arylidene)hydrazine-1-carboxylates †‡

et al. 2021

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Single-step synthesis and in vitro anti-mycobacterial activity of novel nitrofurantoin analogues

Cited by 17 publications

References 52 publications

In Vitro and In Vivo Trypanocidal Efficacy of Synthesized Nitrofurantoin Analogs

In Vitro and In Vivo Trypanocidal Efficacy of Synthesized Nitrofurantoin Analogs

Surface Immobilization of Oxidized Carboxymethyl Cellulose on Polyurethane for Sustained Drug Delivery

Synthesis and fungicidal activity of methyl (E)-1-(2-((E)-2-methoxy-1-(methoxyimino)-2-oxoethyl)benzyl)-2-(1-arylidene)hydrazine-1-carboxylates †‡

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