Diversity-oriented sustainable synthesis of antimicrobial spiropyrrolidine/thiapyrrolizidine oxindole derivatives: New ligands for a metallo-β-lactamase from Klebsiella pneumonia

Dandia, Anshu; Khan, Shahnawaz; Soni, Pragya; Indora, Aayushi; Mahawar, Dinesh Kumar; Pandya, Prateek; Chauhan, Chetan Singh

doi:10.1016/j.bmcl.2017.04.083

Cited by 38 publications

(15 citation statements)

References 47 publications

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“…3 ) with novel mechanism of action (inhibitors of glutamate racemase) against Clostridium difficile 46 and as inhibitors ( 7a-d ; Fig. 3 ) of metallo-β-lactamase 47 have been identified through the DOS approach. Compound 6 (BRD0761) has greater potency against several C. difficile isolates (MIC of 0.06–1 µg/mL) than vancomycin.…”

Section: New Structures For Old Molecular Targets: “A Good Target Is mentioning

confidence: 99%

“…They allow for preparation of libraries of compounds through relatively few chemical transformations in a highly divergent manner. 22,[37][38][39][40][41][42][43][44][45][46][47][48][49][50][51] The DOS [38][39][40][41][42][43][44][45][46][47] and CtD 22,[49][50][51] are directed toward addressing the specific requirements for a successful antibacterial structure. As mentioned earlier, average log D values (log P or log D values are the parameters for measuring hydrophobicity) for drugs targeting these organisms are −0.2 and −2.8, respectively, and 1.6 for other drugs.…”

Section: New Structures For Old Molecular Targets: "A Good Target Is mentioning

confidence: 99%

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Addressing Antimicrobial Resistance through New Medicinal and Synthetic Chemistry Strategies

Konaklieva

2019

SLAS Discovery

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Over the past century, a multitude of derivatives of structural scaffolds with established antimicrobial potential have been prepared and tested, and a variety of new scaffolds have emerged. The effectiveness of antibiotics, however, is in sharp decline because of the emergence of drug-resistant microorganisms. The prevalence of drug resistance, both in clinical and community settings, is a consequence of bacterial ingenuity in altering pathways and/or cell morphology, making it a persistent threat to human health. The fundamental ability of pathogens to survive in a multitude of habitats can be triggered by recognition of chemical signals that warn organisms of exposure to a potentially harmful environment. Host immune defenses, including reactive oxygen intermediates and antibacterial substances, are among the multitude of chemical signals that can subsequently trigger expression of phenotypes better adapted for survival in that hostile environment. Thus, resistance development appears to be unavoidable, which leads to the conclusion that developing an alternative perspective for treatment options is vital. This review will discuss emerging medicinal chemistry approaches for addressing the global multidrug resistance in the 21st century.

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Section: New Structures For Old Molecular Targets: “A Good Target Is mentioning

confidence: 99%

Section: New Structures For Old Molecular Targets: "A Good Target Is mentioning

confidence: 99%

Addressing Antimicrobial Resistance through New Medicinal and Synthetic Chemistry Strategies

Konaklieva

2019

SLAS Discovery

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“…Various MBL inhibitors have been reported. The key structural feature of these inhibitors includethetrifluoromethyl alcohol and ketone [25], dicarboxylic acids [26,27], thiols [28], sulfates [29], hydroxamates [30], tetrazoles [31], and sulfonamides [32]. This review focuses on the new inhibitors against MBLs, covering the literature from 2007 till now.…”

Section: Introductionmentioning

confidence: 99%

The Development of New Small-Molecule Inhibitors Targeting Bacterial Metallo-β-lactamases

Wang

Cheng

Liu

et al. 2018

CTMC

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Metallo-β-lactamases (MBLs) are a family of Zn(II)-dependent enzymes that can hydrolyze almost all β-lactam antibiotics. Horizontal transfer of the genes encoding MBLs among Gram-negative bacteria pathogens has led to the emergence of extensively drug-resistant pathogens, which now represent a major threat to human health. As there is not to date yet a clinically available MBL inhibitor, the discovery of new MBL inhibitors has great urgency. This review highlights the recent developments in the discovery of small-molecule MBL inhibitors.

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“…To the best of our knowledge, there seems to be no report on the synthesis of spiroheterocycles incorporating these three pharmacophoric moieties in [TMG][Ac] IL as the green reaction media. In continuation of our ongoing program in the development of greener and sustainable process for the synthesis of spirooxindoles and our expertise in ILs mediated heterocyclic synthesis , herein, we wish to report for the first time, a highly efficient and sustainable approach for the construction of medicinally important novel spirooxindoles using task‐specific [TMG][Ac] IL as the recyclable solvent.…”

mentioning

confidence: 99%

Task‐specific Ionic Liquid Mediated Eco‐compatible Approach for the Synthesis of Spirooxindole Derivatives and Their DNA Cleavage Activity

Dandia

Jain

Sharma

et al. 2018

Journal of Heterocyclic Chem

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Guanidine‐based task‐specific ionic liquid 1,1,3,3‐tetramethylguanidine acetate [TMG][Ac]was found to be a very effective solvent for the synthesis of pharmaceutically important spirooxindole derivatives through one‐pot multicomponent reaction of substituted isatin, thiazolidine‐4‐carboxylic acid and naphthoquinone followed by the spontaneous dehydrogenation in excellent yields without using any reagent and catalyst. The TMG‐based ionic liquid could be recovered and used at least four times without considerable reduction in its activity. The advantageous features of the developed synthetic protocol are high atom economy, operational simplicity, shorter reaction time, easily handling, and environmentally benign. The structure and relative stereochemistry of final products was established by single crystal X‐ray structure and spectroscopic techniques. The synthesized compounds were subjected for DNA cleavage activity.

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Diversity-oriented sustainable synthesis of antimicrobial spiropyrrolidine/thiapyrrolizidine oxindole derivatives: New ligands for a metallo-β-lactamase from Klebsiella pneumonia

Cited by 38 publications

References 47 publications

Addressing Antimicrobial Resistance through New Medicinal and Synthetic Chemistry Strategies

Addressing Antimicrobial Resistance through New Medicinal and Synthetic Chemistry Strategies

The Development of New Small-Molecule Inhibitors Targeting Bacterial Metallo-β-lactamases

Task‐specific Ionic Liquid Mediated Eco‐compatible Approach for the Synthesis of Spirooxindole Derivatives and Their DNA Cleavage Activity

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