Biochemical and microbiological evaluation of <i>N</i>-aryl urea derivatives against mycobacteria and mycobacterial hydrolases

Vartak, Abhishek; Goins, Christopher M.; Moura, Vinicius Calado Nogueira de; Schreidah, Celine M.; Landgraf, Alexander D.; Lin, Boren; Du, Jianyang; Jackson, Mary; Ronning, Donald R.; Sucheck, Steven J.

doi:10.1039/c9md00122k

Cited by 11 publications

(5 citation statements)

References 37 publications

(46 reference statements)

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“…Only the 4e compound, shown in Table 2, exhibited a moderate MIC of 25 µM, while the toxicity analysis performed over murine cells showed a higher MIC. Despite these preliminary results, this study is a valuable starting point for the development of effective Mab hydrolase inhibitors [62]. Another important target involved in cell wall biosynthesis is the enoyl-ACP reductase (InhA), which is involved in mycolic acid biosynthesis [64].…”

Section: Other Inhibitors Of the Cell Wall Metabolismmentioning

confidence: 98%

“…Rv3802c belongs to a gene cluster that modulates mycolic acid biosynthesis and transport. Recent studies have confirmed that this enzyme hydrolyses the phosphatidylinositol, regulating the membrane lipid content [62]. Considering the importance of his role in cells, Rv3802c has been taken into consideration as a putative drug target to kill mycobacteria.…”

Section: Other Inhibitors Of the Cell Wall Metabolismmentioning

confidence: 99%

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Moles of Molecules against Mycobacterium abscessus: A Review of Current Research

Cocorullo,

Bettoni,

Foiadelli

et al. 2023

Future Pharmacology

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Mycobacterium abscessus is an emerging opportunistic pathogen that infects mainly the respiratory tract of individuals with pre-existing clinical pictures. In recent years, the incidence of infections of this microorganism has risen, in particular in patients with cystic fibrosis, leading to an exacerbation of their conditions. The actual therapeutic regimen has low efficacy and is extended for long periods since it is mainly based on a combination of repurposed drugs, generally from treatments of Mycobacterium tuberculosis infections. For this reason, it is necessary to develop new drugs or alternative strategies in order to improve the efficacy and shorten the time of treatments. This review aims to give an overview of drugs in the pre-clinical and clinical phases of evaluation against M. abscessus and the molecules that have been in development for the past five years in the early drug-discovery phase.

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Section: Other Inhibitors Of the Cell Wall Metabolismmentioning

confidence: 98%

Section: Other Inhibitors Of the Cell Wall Metabolismmentioning

confidence: 99%

Moles of Molecules against Mycobacterium abscessus: A Review of Current Research

Cocorullo,

Bettoni,

Foiadelli

et al. 2023

Future Pharmacology

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“…We synthesized derivative FAM-DA-3CH2 in two steps (Scheme ). At first, alkyne 1 was obtained from furfuryl isocyanate, which is commercially available or otherwise readily accessible from furfurylamine . Second, using the Hay catalyst, we achieved the homocoupling reaction of the terminal alkyne 1 in 2 h 30 min to give the desired diacetylene.…”

Section: Synthesismentioning

confidence: 99%

Crystal Structures of Lignocellulosic Furfuryl Biobased Polydiacetylenes with Hydrogen-Bond Networks: Influencing the Direction of Solid-State Polymerization through Modification of the Spacer Length

Baillargeon

Robidas

Toulgoat

et al. 2022

Crystal Growth & Design

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We present the topochemical polymerization of two lignocellulosic biobased diacetylenes (DAs) that only differ by an alkyl spacer length of 1 methylene (n = 1) or 3 methylene units (n = 3) between the diyne and carbamate functionalities. Their crystalline molecular organizations have the distinctive feature of being suitable for polymerization in two potential directions, either parallel or skewed to the hydrogen-bonded (HB) network. However, single-crystal structures of the final polydiacetylenes (PDAs) demonstrate that the resulting orientation of the conjugated backbones is different for these two derivatives, which lead to HB supramolecular polymer networks (2D nanosheets) for n = 1 and to independent linear PDA chains with intramolecular HBs for n = 3. Thus, spacer length modification can be considered a new strategy to influence the molecular orientation of conjugated polymer chains, which is crucial for developing the next generation of materials with optimal mechanical and optoelectronic properties. Calculations were performed on model oligodiacetylenes to evaluate the cooperativity effect of HBs in the different crystalline supramolecular packing motifs and the energy profile related to the torsion of the conjugated backbone of a PDA chain (i.e., its ability to adopt planar or helical conformations).

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“…An independent research group reported on the activity of an N ‐aryl urea derivative (structures not shown) against M. abscessus (MIC value of 25 µM) but the mechanism through which the compound inhibits mycobacterial growth was not determined 192 …”

Section: Interesting Early‐stage Small Molecules Active Against M Abscessus: From Bench To Bedside?mentioning

confidence: 99%

Pipeline of anti‐Mycobacterium abscessus small molecules: Repurposable drugs and promising novel chemical entities

Egorova¹,

Jackson

Gavrilyuk³

et al. 2021

Medicinal Research Reviews

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The Mycobacterium abscessus complex is a group of emerging pathogens that are difficult to treat. There are no effective drugs for successful M. abscessus pulmonary infection therapy, and existing drug regimens recommended by the British or the American Thoracic Societies are associated with poor clinical outcomes. Therefore, novel antibacterial drugs are urgently needed to contain this global threat. The current anti‐M. abscessus small‐molecule drug development process can be enhanced by two parallel strategies—discovery of compounds from new chemical classes and commercial drug repurposing. This review focuses on recent advances in the finding of novel small‐molecule agents, and more particularly focuses on the activity, mode of action and structure–activity relationship of promising inhibitors from five different chemical classes—benzimidazoles, indole‐2‐carboxamides, benzothiazoles, 4‐piperidinoles, and oxazolidionones. We further discuss some other interesting small molecules, such as thiacetazone derivatives and benzoboroxoles, that are in the early stages of drug development, and summarize current knowledge about the efficacy of repurposable drugs, such as rifabutin, tedizolid, bedaquiline, and others. We finally review targets of therapeutic interest in M. abscessus that may be worthy of future drug and adjunct therapeutic development.

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Biochemical and microbiological evaluation of N-aryl urea derivatives against mycobacteria and mycobacterial hydrolases

Abstract: N-Aryl urea derivatives were synthesized and some showed activity against mycobacterial hydrolases while others showed antimicrobial activity against mycobacterial species.

Cited by 11 publications

References 37 publications

Moles of Molecules against Mycobacterium abscessus: A Review of Current Research

Moles of Molecules against Mycobacterium abscessus: A Review of Current Research

Crystal Structures of Lignocellulosic Furfuryl Biobased Polydiacetylenes with Hydrogen-Bond Networks: Influencing the Direction of Solid-State Polymerization through Modification of the Spacer Length

Pipeline of anti‐Mycobacterium abscessus small molecules: Repurposable drugs and promising novel chemical entities

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