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  • Reddy, N, et al. (author)
  • Neutralizing Carbapenem Resistance by Co-Administering Meropenem with Novel β-Lactam-Metallo-β-Lactamase Inhibitors
  • 2023
  • In: Antibiotics (Basel, Switzerland). - : MDPI AG. - 2079-6382. ; 12:4
  • Journal article (peer-reviewed)abstract
    • Virulent Enterobacterale strains expressing serine and metallo-β-lactamases (MBL) genes have emerged responsible for conferring resistance to hard-to-treat infectious diseases. One strategy that exists is to develop β-lactamase inhibitors to counter this resistance. Currently, serine β-lactamase inhibitors (SBLIs) are in therapeutic use. However, an urgent global need for clinical metallo-β-lactamase inhibitors (MBLIs) has become dire. To address this problem, this study evaluated BP2, a novel beta-lactam-derived β-lactamase inhibitor, co-administered with meropenem. According to the antimicrobial susceptibility results, BP2 potentiates the synergistic activity of meropenem to a minimum inhibitory concentration (MIC) of ≤1 mg/L. In addition, BP2 is bactericidal over 24 h and safe to administer at the selected concentrations. Enzyme inhibition kinetics showed that BP2 had an apparent inhibitory constant (Kiapp) of 35.3 µM and 30.9 µM against New Delhi Metallo-β-lactamase (NDM-1) and Verona Integron-encoded Metallo-β-lactamase (VIM-2), respectively. BP2 did not interact with glyoxylase II enzyme up to 500 µM, indicating specific (MBL) binding. In a murine infection model, BP2 co-administered with meropenem was efficacious, observed by the >3 log10 reduction in K. pneumoniae NDM cfu/thigh. Given the promising pre-clinical results, BP2 is a suitable candidate for further research and development as an (MBLI).
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  • Reddy, N, et al. (author)
  • Neutralizing Carbapenem Resistance by Co-Administering Meropenem with Novel β-Lactam-Metallo-β-Lactamase Inhibitors
  • 2023
  • In: Antibiotics (Basel, Switzerland). - : MDPI AG. - 2079-6382. ; 12:4
  • Journal article (peer-reviewed)abstract
    • Virulent Enterobacterale strains expressing serine and metallo-β-lactamases (MBL) genes have emerged responsible for conferring resistance to hard-to-treat infectious diseases. One strategy that exists is to develop β-lactamase inhibitors to counter this resistance. Currently, serine β-lactamase inhibitors (SBLIs) are in therapeutic use. However, an urgent global need for clinical metallo-β-lactamase inhibitors (MBLIs) has become dire. To address this problem, this study evaluated BP2, a novel beta-lactam-derived β-lactamase inhibitor, co-administered with meropenem. According to the antimicrobial susceptibility results, BP2 potentiates the synergistic activity of meropenem to a minimum inhibitory concentration (MIC) of ≤1 mg/L. In addition, BP2 is bactericidal over 24 h and safe to administer at the selected concentrations. Enzyme inhibition kinetics showed that BP2 had an apparent inhibitory constant (Kiapp) of 35.3 µM and 30.9 µM against New Delhi Metallo-β-lactamase (NDM-1) and Verona Integron-encoded Metallo-β-lactamase (VIM-2), respectively. BP2 did not interact with glyoxylase II enzyme up to 500 µM, indicating specific (MBL) binding. In a murine infection model, BP2 co-administered with meropenem was efficacious, observed by the >3 log10 reduction in K. pneumoniae NDM cfu/thigh. Given the promising pre-clinical results, BP2 is a suitable candidate for further research and development as an (MBLI).
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  • Chetty, LC, et al. (author)
  • Organic Base-Mediated Carboxylation of (Hetero)aromatic Compounds Using Supercritical Carbon Dioxide (scCO(2))
  • 2022
  • In: SYNTHESIS-STUTTGART. - : Georg Thieme Verlag KG. - 0039-7881. ; 54:21, s. 4827-4833
  • Journal article (other academic/artistic)abstract
    • A straightforward site-selective method for the direct carboxylation of resorcinols (3-hydroxyphenol derivatives), phenols, and indoles is reported. The products were obtained in moderate to high yields using supercritical carbon dioxide as an electrophile and solvent under basic conditions. This method offers solvent and metal free conditions without the cumbersome exclusion of air or water with convenient purification.
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  • Chinthakindi, PK, et al. (author)
  • On-Water Synthesis of Biaryl Sulfonyl Fluorides
  • 2016
  • In: The Journal of organic chemistry. - : American Chemical Society (ACS). - 1520-6904 .- 0022-3263. ; 81:6, s. 2618-2623
  • Journal article (peer-reviewed)
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  • Rajbongshi, KK, et al. (author)
  • Microwave-Accelerated N -Acylation of Sulfoximines with Aldehydes under Catalyst-Free Conditions
  • 2020
  • In: SYNTHESIS-STUTTGART. - : Georg Thieme Verlag KG. - 0039-7881. ; 52:8, s. 1279-1286
  • Journal article (other academic/artistic)abstract
    • An efficient catalyst-free radical cross-coupling reaction between aromatic aldehydes and sulfoximines was developed. The reaction took place in the presence of N-bromosuccinimide as the radical initiator under microwave irradiation to afford the corresponding acylated sulfoximines in moderate to excellent yields (27 examples). This protocol proved to be rapid, easy to handle, and applicable to a broad scope of substrates.
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  • Somboro, AM, et al. (author)
  • NOTA: a potent metallo-β-lactamase inhibitor
  • 2015
  • In: The Journal of antimicrobial chemotherapy. - : Oxford University Press (OUP). - 1460-2091 .- 0305-7453. ; 70:5, s. 1594-1596
  • Journal article (other academic/artistic)
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  • Chinthakindi, Praveen Kumar, et al. (author)
  • Sulfonimidamides in Medicinal and Agricultural Chemistry
  • 2017
  • In: Angewandte Chemie International Edition. - : Wiley. - 1433-7851. ; 56:15, s. 4100-4109
  • Journal article (peer-reviewed)abstract
    • The synthesis and evaluation of structural analogues and isosteres are of central importance in medicinal and agricultural chemistry. The sulfonamide functional group represents one of the most important amide isosteres in contemporary drug design, and about 500 such compounds have overcome both the pharmacological and regulatory hurdles that precede studies in humans. The mono aza analogues of sulfonamides, that is, sulfonimidamides, are rapidly gaining popularity as a novel functional group among synthetic chemists involved in the design of biologically active compounds for both pharmaceutical and agrochemical applications. Herein, we review these recent developments to showcase the promise of this functional group.
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  • Result 1-36 of 36

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