Bioactive amide and α-aminophosphonate inhibitors for methicillin-resistant Staphylococcus aureus (MRSA)

Boshta, Nader M.; El-Gamal, E.; El-Sayed, Ibrahim E.T.

doi:10.1007/s00706-018-2303-y

Cited by 17 publications

(11 citation statements)

References 33 publications

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“…An important strategy in fighting antibiotic resistance is the discovery, development of novel antibiotics, and increasing the efficacy of the antibiotic that is already in a clinical study [ 7 ]. In this context, α-aminophosphonates gained great interest by medicinal chemists because of their diverse biological and industrial applications such as antibacterial [ 8 , 9 , 10 , 11 , 12 ], anticancer [ 13 , 14 , 15 ], enzyme inhibitors [ 16 , 17 ], and chelating material [ 18 , 19 , 20 , 21 ] which made them a promising drug candidate for further optimization. These compounds are phosphorus analogs of naturally occurring α-amino acids and therefore, are considered promising in the field of drug discovery and development [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Experimental and Molecular Docking Studies of Cyclic Diphenyl Phosphonates as DNA Gyrase Inhibitors for Fluoroquinolone-Resistant Pathogens

et al. 2022

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DNA gyrase and topoisomerase IV are proven to be validated targets in the design of novel antibacterial drugs. In this study, we report the antibacterial evaluation and molecular docking studies of previously synthesized two series of cyclic diphenylphosphonates (1a–e and 2a–e) as DNA gyrase inhibitors. The synthesized compounds were screened for their activity (antibacterial and DNA gyrase inhibition) against ciprofloxacin-resistant E.coli and Klebsiella pneumoniae clinical isolates having mutations (deletion and substitution) in QRDR region of DNA gyrase. The target compound (2a) that exhibited the most potent activity against ciprofloxacin Gram-negative clinical isolates was selected to screen its inhibitory activity against DNA gyrase displayed IC50 of 12.03 µM. In addition, a docking study was performed with inhibitor (2a), to illustrate its binding mode in the active site of DNA gyrase and the results were compatible with the observed inhibitory potency. Furthermore, the docking study revealed that the binding of inhibitor (2a) to DNA gyrase is mediated and modulated by divalent Mg2+ at good binding energy (–9.08 Kcal/mol). Moreover, structure-activity relationships (SARs) demonstrated that the combination of hydrazinyl moiety in conjunction with the cyclic diphenylphosphonate based scaffold resulted in an optimized molecule that inhibited the bacterial DNA gyrase by its detectable effect in vitro on gyrase-catalyzed DNA supercoiling activity.

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Section: Introductionmentioning

confidence: 99%

Experimental and Molecular Docking Studies of Cyclic Diphenyl Phosphonates as DNA Gyrase Inhibitors for Fluoroquinolone-Resistant Pathogens

et al. 2022

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“…α-Aminophosphonates were thoroughly studied in recent years due to their wide range of environmental [2,3] and biological applications as antitumor, antimicrobial, antibacterial and antiviral agents. [4][5][6] The Kabachnic-Field method is a three-component condensation reaction of primary or secondary amines, carbonyl compound, and dialkylphosphite, and represents a convenient choice for the synthesis of α-aminophosphonates. [7,8] In general, this threecomponent reaction may be carried out by the hydrophosphorylation of a Schiff base amine, which is catalyzed by an acid or base.…”

Section: Introductionmentioning

confidence: 99%

Highly Efficient One‐pot Aerobic Synthesis of α‐Aminophosphonate from Alcohols: Dual Catalytic Effect of Tetrabutylammonium Tribromide (TBATB)

2022

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In this work, a simple, metal-free, and homogeneous two steps one-pot method for the synthesis of α-aminophosphonate in the presence of tetrabutylammonium tribromide (TBATB) from alcohol was reported. Interestingly TBATB showed catalytic effect for both photo tuanable aerobic oxidation of alcohol (including electron rich and poor) and α-aminophosphonate synthesis from in situ prepared aldehyde. Also, more interest-ingly efficiency of the synthesis is higher for starting from alcohols than aldehyde. The optimized condition including: solvent, catalyst amounts, photo and thermal factors was considered. Various derivatives of benzyl alcohol and aniline participated well in this reaction and produced the corresponding α-aminophosphonates efficiently.

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“…α -Aminophosphonates are an important class of amino acid analogues ( Mucha et al, 2011 ) with diverse applications, in medicinal chemistry, agriculture and other industries, as synthetic intermediates with interesting pharmacological properties ( Gemmill et al, 2005 ; Dinér and Amedjkouh, 2006 ; Juribasic et al, 2011 ; Tusek-Bozic, 2013 ; Boshta et al, 2018 ; Imam et al, 2018 ). They have been reported to inhibit enzymes involved in amino acid metabolism, thus having a direct influence on cell functions ( Naydenova et al, 2010 ).…”

Section: Introductionmentioning

confidence: 99%

Theoretical exploration on structures, bonding aspects and molecular docking of α-aminophosphonate ligated copper complexes against SARS-CoV-2 proteases

et al. 2022

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Recent years have witnessed a growing interest in the biological activity of metal complexes of α-aminophosphonates. Here for the first time, a detailed DFT study on five α-aminophosphonate ligated mononuclear/dinuclear CuII complexes is reported using the dispersion corrected density functional (B3LYP-D2) method. The electronic structures spin densities, FMO analysis, energetic description of spin states, and theoretical reactivity behaviour using molecular electrostatic potential (MEP) maps of all five species are reported. All possible spin states of the dinuclear species were computed and their ground state S values were determined along with the computation of their magnetic coupling constants. NBO analysis was also performed to provide details on stabilization energies. A molecular docking study was performed for the five complexes against two SARS-CoV-2 coronavirus protein targets (PDB ID: 6LU7 and 7T9K). The docking results indicated that the mononuclear species had a higher binding affinity for the targets compared to the dinuclear species. Among the species investigated, species I showed the highest binding affinity with the SARS-CoV-2 Omicron protease. NPA charge analysis showed that the heteroatoms of model species III had a more nucleophilic nature. A comparative study was performed to observe any variations and/or correlations in properties among all species.

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Bioactive amide and α-aminophosphonate inhibitors for methicillin-resistant Staphylococcus aureus (MRSA)

Cited by 17 publications

References 33 publications

Experimental and Molecular Docking Studies of Cyclic Diphenyl Phosphonates as DNA Gyrase Inhibitors for Fluoroquinolone-Resistant Pathogens

Experimental and Molecular Docking Studies of Cyclic Diphenyl Phosphonates as DNA Gyrase Inhibitors for Fluoroquinolone-Resistant Pathogens

Highly Efficient One‐pot Aerobic Synthesis of α‐Aminophosphonate from Alcohols: Dual Catalytic Effect of Tetrabutylammonium Tribromide (TBATB)

Theoretical exploration on structures, bonding aspects and molecular docking of α-aminophosphonate ligated copper complexes against SARS-CoV-2 proteases

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